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(11) EP 2 326 338 B1

(12) EUROPEAN PATENT SPECIFICATION

(45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 36/47 (2006.01) A61K 36/23 (2006.01) 05.08.2015 Bulletin 2015/32 A61K 36/89 (2006.01) A61K 36/37 (2006.01) A61K 36/48 (2006.01) A61K 36/906 (2006.01) (2006.01) (2006.01) (21) Application number: 09741450.2 A61K 36/29 A61K 36/22 A61K 36/72 (2006.01) A61K 36/59 (2006.01) A61K 36/899 (2006.01) (22) Date of filing: 17.09.2009

(86) International application number: PCT/IN2009/000510

(87) International publication number: WO 2010/032267 (25.03.2010 Gazette 2010/12)

(54) A HERBAL FORMULATION FOR PREVENTION AND TREATMENT OF DIABETES AND ASSOCIATED COMPLICATIONS PFLANZLICHE FORMULIERUNG ZUR PRÄVENTION UND BEHANDLUNG VON DIABETES UND RELEVANTEN KOMPLIKATIONEN FORMULATION À BASE DE PLANTES POUR LA PRÉVENTION ET LE TRAITEMENT DU DIABÈTE ET DE COMPLICATIONS ASSOCIÉES

(84) Designated Contracting States: GB-A- 190 505 856 JP-A- 10 127 256 AT BE BG CH CY CZ DE DK EE ES FI FR GB GR JP-A- 2000 080 044 JP-A- 2005 053 864 HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL JP-A- 2005 320 281 JP-A- 2006 008 528 PT RO SE SI SK SM TR JP-A- 2006 056 836 JP-A- 2006 104 094 JP-A- 2006 232 781 JP-A- 2007 097 500 (30) Priority: 22.09.2008 IN DE22212008 US-A- 4 826 684 US-A- 4 908 207 15.06.2009 IN DE12212009 US-A1- 2004 116 394 US-A1- 2006 018 978 15.06.2009 IN DE12222009 US-A1- 2008 206 372 15.06.2009 IN DE12232009 15.06.2009 IN DE12242009 • DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, (43) Date of publication of application: US; January 2002 (2002-01), ARUN N ET AL: 01.06.2011 Bulletin 2011/22 "Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats" XP002572901 (73) Proprietor: Innoveda Biological Solutions (P) Ltd. Database accession no. PREV200200203967 Greater Kailash II, New Delhi-110 048 (IN) cited in the application • DATABASE EMBASE [Online] ELSEVIER (72) Inventor: KRISHNAN, G. Geetha SCIENCE PUBLISHERS, AMSTERDAM, NL; 1990, Patparganj, Delhi 110092 (IN) TANK R ET AL: "Antidiabetic activity of Curcuma longa (50% EtOh-extr.) in alloxan induced (74) Representative: Winter, Brandl, Fürniss, Hübner, diabetic rats" XP002572902 Database accession Röss, Kaiser, Polte - Partnerschaft mbB no. EMB-1990339134 Patent- und Rechtsanwaltskanzlei • DATABASE BIOSIS [Online] BIOSCIENCES Alois-Steinecker-Strasse 22 INFORMATION SERVICE, PHILADELPHIA, PA, 85354 Freising (DE) US; 15 September 1999 (1999-09-15), RANA T S ET AL: "Studies on indigenous herbal remedies (56) References cited: for diabetes mellitus in India" XP002572903 EP-A1- 1 723 960 EP-A1- 1 925 310 Database accession no. PREV200000163003

Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 326 338 B1

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• DATABASE BIOSIS [Online] BIOSCIENCES • MURALI Y K ET AL: "Antihyperglycemic effect of INFORMATION SERVICE, PHILADELPHIA, PA, water extract of dry fruits of US; April 1997 (1997-04), SHARMA S R ET AL: in experimental diabetes mellitus", MEDICINAL & "Hypoglycaemic potential of Mangifera indica AROMATIC ABSTRACTS, SCIENTIFIC leaves in rats" XP002572904 Database accession PUBLISHERS, SCIENTIFIC PUBLISHERS, NEW no. PREV199800082356 cited in the application DELHI - INDIA, vol. 27, no. 2, 1 March 2005 • DATABASE WPI Week 200338 Thomson (2005-03-01), XP018004409, ISSN: 0250-4367 Scientific, London, GB; AN 2003-400672 • DATABASE BIOSIS [Online] BIOSCIENCES XP002575883 & RU 2 197 259 C1 (BUZLAMA V S) INFORMATION SERVICE, PHILADELPHIA, PA, 27 January 2003 (2003-01-27) US 2007 SENTHILKUMAR G P ET AL: ’Evaluation • DATABASE WPI Week 200904, Derwent of antioxidant potential of Terminalia chebula Publications Ltd., London, GB; AN 2009- A87141, fruits studied in streptozotocin- induced diabetic XP002575884 & KR 10 0 814 368 B1 (UNIV KOREA rats’Database accession no. PREV200700545382 IND & ACADEMIC COLLABORATION) 18 March & PHARMACEUTICAL BIOLOGY, vol. 45, no. 6, 2008 2007, pages 511-518, ISSN: 1388-0209, DOI: • DATABASE WPI Week 200419 Thomson 10.1080/13880200701446720 Scientific, London, GB; AN 2004-192362 XP002575885 & CN 1 444 939 A (SHENZHEN Remarks: CHINESE TRADITIONAL MEDICINE &) 1 October Thefile contains technical information submitted after 2003 (2003-10-01) the application was filed and not included in this • DATABASE WPI Week 200415 Thomson specification Scientific, London, GB; AN 2004-144588 XP002575886 & CN 1 456 259 A (MAO Y) 19 November 2003 (2003-11-19) • DATABASE WPI Week 200803, Derwent Publications Ltd., London, GB; AN 2008- A43864, XP002575904 & KR 2007 074 066 A (CHOI S G) 12 July 2007

2 1 EP 2 326 338 B1 2

Description proves the cell’s sensitivity to the presence of insulin, thereby improving the uptake of glucose into the Field of the invention cells, leading to better blood sugar control.

[0001] The present invention relates to an herbal for- 5 iii) Insulin:-This is exogenously supplemented in the mulation for the prevention and treatment of diabetes and case of people suffering from both type I and type II the associated complications.. The present invention diabetes. particularlyrelates to an herbal formulation useful for con- trolling / reducing the blood glucose level significantly [0008] Diabetes is a lifestyle disease and cannot be and for the prevention / management / treatment of dia- 10 cured. The current therapies mentioned above are there- betes related complications. The formulation of the fore only a blood sugar management mechanism. As di- present invention not only efficiently controls the Type 2 abetes is a chronic, long-duration disease, these drugs diabetes but also offers reversal possibilities in predia- need to be taken on a sustained basis. Currently, avail- betes and thereby a possible preventive option for Type able synthetic drugs suffer from concomitant side effects 2 diabetes mellitus and the associated complications. 15 caused due to long duration of usage. Literature survey [0002] The present invention also relates to a herbal indicates that cardiovascular mortality was higher in pa- formulation for the prevention and tratement of diabetes tients with oral hypoglycemics than in those treated with mellitus. diet and exercise alone or with insulin. Sulphonylureas [0003] The present invention also relates to a herbal cause hypoglycemia as a side effect. Biguanides cause formulation for prevention and treatment of renal compli- 20 lactic acidosis. Oral hypoglycemia-drugs also cause GIT cations associated with diabetes consequently reducing irritation, weight gain, hypertension, etc. On continuous the serum creatinine levels, which is elevated due to rea- and constant exertion, the diabetic person is also liable sons which can be attributed to the kidneys and their for pancreatic fatigue. In addition, it is also seen that many functional and structural integrity. of the existing drugs available lead to drug resistance in [0004] The present invention also relates to a herbal 25 patients with long durations of use. formulation for the prevention and treatment of retinop- [0009] The long-term complications of diabetes are athy associated with diabetes. The formulation of the more damaging. This is caused by spikes in blood sugar present invention not only efficiently controls thein patients during the day. Increased blood sugar even progress of diabetic retinopathy but also offers reversal for short periods leads to glycosylation of Hemoglobin. possibilities in such cases. 30 Glycosylated Hemoglobin causes long-term irreversible [0005] The present invention also relates to a herbal damages to eyes, kidneys, nerves and blood vessels. formulation for prevention and treatment of oxidative [0010] A wide-spread pathological complication of Di- damage to heart and its blood vessels associated with abetes is thickening of capillary basement membrane, diabetes useful for reducing oxidative damage caused increase in vessel wall matrix and cellular proliferation to the cardiac musculature and blood vessel walls, and 35 resulting in vascular complications like lumen narrowing, treating hypertension. early atherosclerosis, and sclerosis of glomerular capil- [0006] Diabetes Mellitus is the most prevalent meta- laries, retinopathy, neuropathy and peripheral vascular bolic disorder among humans with enormous implica- insufficiency. The level of glycosylated hemoglobin tions on social health and financial wealth. This is char- (HbA1c) is also increased in diabetes and is taken as an acterized by poor regulation of blood glucose levels in 40 index of protein glycosylation. It reflects the state of gly- human beings. Other than blood glucose levels the long caemia over the preceding 2 - 3 months. As such, there term effects of the disease involves all major systems is no drug available for the treatment of diabetic compli- and organs of the body including the Heart and blood cations. vessels, Kidneys, Liver, Eyes and the nervine systems. [0011] Further, diseases of the kidneys are very com- The improper nutrition of the cells due to lack of insulin, 45 mon now a days and it also occurs as complications or leads to structural and functional irregularities in the cells, secondary to chronic diseases such as diabetes and including the waste they generate and its management. heart diseases. Elevation of serum creatinine is a major Diabetes mellitus also predisposes cardiac failure and parameter to identify the structural and functional health renal failure. of the kidneys. There are no medicines available as on [0007] Presently, this disorder is managed by taking 50 todaywhich can improve the health of thedefunct kidneys drugs falling into the following categories: and thereby decrease the creatinine levels. [0012] Diabetic eye disease refers to a group of eye i) pancreatic stimulators: - This class of drugs helps problems that people with diabetes may face as a com- to stimulate the pancreas, leading to increased se- plication of diabetes. All can cause severe vision loss or cretion of insulin. This addresses the diabetes55 even blindness. caused by inadequate insulin secretion. [0013] Diabetic eye disease may include:

ii) Insulin sensitizers:- This category of drugs im- Diabetic retinopathy-damage to the blood vessels

3 3 EP 2 326 338 B1 4

in the retina. resistance. Cataract-clouding of the eye’s lens. Cataracts de- iii) that can help in prevention, management and velop at an earlier age in people with diabetes. treatment of diabetic retinopathy. This drug should Glaucoma-increase in fluid pressure inside the lend itself safe for long-term use without any side eye that leads to optic nerve damage and loss of 5 effects and without developing resistance. vision. A person with diabetes is nearly twice as likely iv) that can help in the management of hypertension to get glaucoma as other adults. and simultaneously act as a cardiac protective anti- oxidant. This drug should lend itself safe for long- [0014] Diabetic retinopathy is the most common dia- term use without any side effects and without devel- betic eye disease and a leading cause of blindness in 10 oping resistance American adults. It is caused by changes in the blood vessels of the retina. In some people with diabetic retin- Prior art opathy, blood vessels may swell and leak fluid. In other people, abnormal new blood vessels grow on the surface [0020] For centuries, specific plants, their extracts or of the retina. Blood vessels damaged from diabetic retin- 15 mixtures thereof have been used for treatment of illness- opathy can cause vision loss in two ways: es in Indian system of medicine and many of them have [0015] All people with diabetes-both type 1 and type been documented as having clinical effectiveness in 2--are at risk. The longer someone has diabetes, the treating diabetes. The plants like Alfalfa, Aloe Vera, Bur- more likely he or she will get diabetic retinopathy. Be- dock, Celery, Comsilk, Damiana, Elecampane, Eucalyp- tween 40 to 45 percent of pateints diagnosed with dia- 20 tus, Fenugreek, Garlic, Ginger, Ginseng, Panax, Juniper, betes have some stage of diabetic retinopathy. Today, Marshmallow, Myrrh, Nettle, Sage, Tansy which are all diabetic retinopathy is treated only with laser at the last part of daily food ingredients have been also reported as stage of the disease. No medicine is available to manage hypoglycemic herbal ingredients. and treat the same before such condition ensues. [0021] Patent Application no. EP20050779434 teach- [0016] Hypertension, also referred to as high blood 25 es the invention provides an herbal composition compris- pressure, is a medical condition in which the blood pres- ing a extract from Azadirachta indica, Aloe vera and sure is chronically elevated. In current usage, the word cinnamon, useful for the treatment of diabetes and type "hypertension" without a qualifier normally refers to sys- II diabetes associated complications such as atheroscle- temic, arterial hypertension. rosis, hypertension, diabetic retinopathy, diabetic neph- [0017] Persistent hypertension is one of the risk factors 30 ropathy, diabetic polyneuropathies, thyroid disorders, leg for strokes, heart attacks, heart failure and arterial aneu- ulcers, diabetic foot and liver diseases, and for improving rysm, and is a leading cause of chronic renal failure. Even the immune function in a diabetic patient. moderate elevation of arterial blood pressure leads to [0022] Patent Application no. KR20020011015 teach- shortened life expectancy. At severely high pressures, es An orient herbal medicinal formulation for the treat- defined as mean arterial pressures 50% or more above 35 ment of diabetes is provided. The formulation has espe- average, a person can expect to live no more than a few cially curative and preventive effect for the insulin non- years unless appropriately treated. Beginning at a systo- dependent diabetes(type 2 diabetes) and its complica- lic pressure of 115 mm Hg and diastolic pressure of 75 tion as well as insulin dependent diabetes(type 1 diabe- mm Hg (commonly written as 115/75 mm Hg),cardiovas- tes) by lowering sugar content in the body. It also has cular disease (CVD) risk doubles for each increment of 40 excellent effect as a toner for the weak liver, kidney, stom- 20/10 mm Hg. ach, lung and heart and as body stamina. CONSTITU- [0018] All drug treatments for hypertension have side TION: The formulation comprises: Euonymus alatus effects, and while the evidence of benefit at higher blood (Thumb) Sieb; balsam pear; Lycium root; corn filament; pressures is overwhelming, drug trials to lower moder- Salviae Radix; white Atractylis; Curcuma longa Rhizoma; ately-elevated blood pressure have failed to reduce over- 45 white agaric; Alisma; Cuscuta seed; root peel of Paeonia all death rates. moutan Sims in a weight ratio of 30: 10: 10: 10: 5: 5: 5: [0019] Consequently, the need of the hour is to develop 7: 5: 5: 3, respectively. The cleaned Euonymus alatus safe and efficacious drugs: (Thumb) Sieb is put into distilled water and the solution is made pH9 by adding NaOH, boiled under pressure for i) that can help in the management of blood sugar 50 3 hours, filtered, concentrated, dried under vacuum, levels and associated complications in diabetes mel- ground and made powder by screening more than 100 litus patients. This drug should lend itself safe for times. The cleaned corn filament is fermented at long-term use without any side effects and without 50deg.C(with addition of yeast), separated from unwant- developing resistance. ed material, boiled under pressure with distilled water of ii) that can help in the improving the renal health and 55 5 times for 3 hours, filtered, concentrated, dried under thereby also reduce the elevated levels of serum cre- vacuum and made powder by screening more than 100 atinine. This drug should lend itself safe for long-term times. Salviae Radix is extracted with 70% ethanol, con- use without any side effects and without developing centrated and dried under vacuum and made powder by

4 5 EP 2 326 338 B1 6 screening more than 100 times. Lycium root, white At- Jaipur which appeared in the Indian Zoologist. v. 12(3-4): ractylis, Curcuma longa Rhizoma, white agaric, Alisma p. 321-322, 1988). It has also been reported that curcu- and Cuscuta seed and root peel of Paeonia moutan Sims min is more effective in attenuating diabetes mellitus than are mixed, distilled water of 5 times is added, boiled 3 turmeric.(Reference is made to the publication titled " the hours under vacuum, concentrated and dried under vac- 5 Effect of turmeric on the enzymes of glucose metabolism uum and made powder by screening more than 100 in diabetic rats and published in the Journal of Herbs, times. Balsam pear is obtained in liquid after freeze ex- Spices and Medicinal Plants. V. 10(1): p. 75-84, 2002 by tracting and concentrating the filtrate. The above pow- Narayannasamy, A.; Namasivayam, N.; Radha, K. of the ders are mixed, screened more than 100 times, added Department of Biochemistry, Annamalai University, An- to the concentrate of balsam pear and freeze dried to 10 namalainagar make the final formulation. [0027] Reference is made to the publication by Arun, [0023] Patent application no. CA2532332 teaches an N.; Nalini, N. of the Department of Biochemistry, An- herbal extract-based composition comprising an extract namalai University, Annamalainagar 608 002, Tamil of Gynostemma pentaphyllum, an extract of Crataegus Nadu, India titled the Efficacy of turmeric on blood sugar pinnatifidia (hawthorn), an extract of Camellia sinensis 15 and polyol pathway in diabetic albino rats published in (green tea), and an extract of Momordica charantia (bitter thePlant Foods for Human Nutrition.V. 57(1): p.141-150, melon). The composition may further comprise an extract 2002 and which reads as "The effect of turmeric ([Cur- of mulberry (Morus species). Also provided is a process cuma longa]) rhizomes and its active principle, curcumin, for preparing a herbal extract-based composition which on alloxan induced diabetes mellitus in a rat model was comprises separately extracting each of hawthorn, green 20 studied. Administration of turmeric or curcumin to diabet- tea, Gynostemma pentaphyllum, mulberry, and bitter ic rats reduced the blood sugar, Hb and glycosylated he- melon; drying extraction eluates obtained from the ex- moglobin levels significantly. Turmeric and curcumin tracting of each of the herbal components to obtain or- supplementation also reduced the oxidative stress en- ganic residues in forming a hawthorn extract powder, countered by the diabetic rats. This was demonstrated green tea extract powder, a Gynostemma pentaphyllum 25 by the lower levels of TBRAS (thiobarbituric acid reactive extract powder, a mulber ry extract powder, and a bitter substances), which may have been due to the decreased melon powder; and combining the green tea extra ct pow- influx of glucose into the polyol pathway leading to an der, the Gynostemma Pentaphyllum extract powder, the increased NADPH/NADP ratio and elevated activity of hawthorn extract powder, the mulberry extract powder, the potent antioxidant enzyme GPx. Moreover, the ac- and the bitter melon powder in desired proportions to 30 tivity of SDH (sorbitol dehydrogenase), which catalyzes form the herbal extract-based composition which, when the conversion of sorbitol to fructose, was lowered sig- taken orally, has health-promoting effects including anti- nificantly on treatment with turmeric or curcumin. These diabetic effects that include, but are not limited to, de- results also appeared to reveal that curcumin was more creasing visceral fat, reducing hyperglycemia, and re- effective in attenuating diabetes mellitus related changes ducing the occurrence and severity of diabetic complica- 35 than turmeric. tions, associated with type 2 diabetes. [0028] Reference is made to the publication by Nalini, [0024] Patent application no WO02089825 teaches a D.; Kapoor, R. Of the Department of Home Science, Sri herbal medicinal composition for preventing or treating Satya Sai Institute of Higher Learning, Anantapur, AP, type II diabetes. The composition is comprised of extracts India Titled Effect of plant fruits - Indian gall nut, bedda from Pterocarpus marsupium, Morus alba, Orthosiphon 40 nut and gooseberry - on hypercholesterolemic rats and aristatus, Opiophogon japonicus, Rosa rugosa, Commel- published by Plant Foods for Human Nutrition. v. 53(4): ina communis, Trichosanthis kirilowii and Anemarrhena p. 343-349, 1999 which reads as The effect of supple- asphodeloides. mentation of three fruits, [Terminalia chebula] (Indian gall [0025] The use of plant extracts and derivatives of nut), [Terminalia belerica], (bedda nut) and [Emblica of- plants for healing and prevention purposes has been de- 45 ficinalis](gooseberry), on serum lipid levels and excretion scribed extensively in traditional and folk medicine liter- of bile acids was investigated. Rats made hypercholes- ature. Over the centuries, plants have served as a major terolemic by feeding hypercholesterolemia inducing diet source of medicines for treating and prevention of dis- (HID) for a period of 30 days were used as the test model. eases of mankind. Although recently the ability for syn- Feeding of a dried powder of these fruits along with the thesis and design of new medicines has provided new 50 HID resulted in significant (p less than 0.01) reduction in pathways for the development of therapeutic drugs; how- total cholesterol, LDL cholesterol and triglycerides. HDL ever, phytomedicines derived from plants still hold a cholesterol remained unchanged in groups fed gall nut strong position. and bedda nut. However, the levels were significantly (p [0026] Curcuma has been used for lowering blood glu- less than 0.01) higher in groups fed mixed and goose- cose level (Reference is made to the publication titled " 55 berry diets in comparison to the control diet. Excretion of Hyperglycemic activity of Curcuma longa of Tank, R.; bile acids was found to be significantly (p less than 0.01) Sharma, N.; Dixit, V.P. of the Reproductive Physiology higher in animals receiving the three fruits in combination Section, Department of Zoology, University of Rajasthan, in comparison to those receiving the individual fruits.

5 7 EP 2 326 338 B1 8

[0029] Reference is made to the publication by Dwive- phus vulgaris var. spinosus, and the fruits and stem bark di, S.; Gupta, D.; Sharma, K.K. of the Preventive Cardi- of Zizyphus jujuba var. inermis in mice which was pub- ology Group, UCMS and GTB Hospital, Delhi 110095, lished in the Yakhak Hoeji. v. 37(2): p. 143-148, 1993 India titled the Modification of coronary risk factors by and reads as The sedative activity of four aporphine al- medicinal plants which appeared in the Journal of Me- 5 kaloids (APA) and nine cyclopeptide alkaloids (CPA), iso- dicinal and Aromatic Plant Sciences. v. 22(1 B): p. lated from the seeds (sanjoin) of Zizyphus vulgaris var. 616-620, 2000 and reads as "Effect of four medicinal spinosus] and the fruits and stem bark of [Zizyphus jujuba plants i.e. [Terminalia arjuna, Emblica officinalis, Oci- var. spinosus] and the fruits and stem bark of [Zizyphus mum sanctum] and [Withania somnifera] was examined. jujuba var. inermis] has been reported. The assessment On risk factors in convalescing patients of coronary artery 10 of sedative activity was carried out, employing a hexo- disease (myocardial infraction angina pectoris) was stud- barbital-induced sleeping time method in mice. When the ied. The drug was adminsitered in a capsule form relative sedative potency of sanjoinine-A (CAP) was giv- (Cardipro) in twice daily dosage. A total of 30 uncompli- en as one unit, those of nuciferine (APA), lysicamine cated coronay artery disease patients were randomly di- (APA), chlorpromazine (positive control) and sanjoinine- vided into two groups A and B of 15 each. Group A pa- 15 Ahl (an epimer of sanjoinine-A) were 13, 6.5,5, and 3 tients were given Cardipro (1 Cap. BD) in addition to con- respectively. The sedative activities of other CPAs were ventional antiischaemic therapy, while Group B patients much lower than those of sanjoinine-A and -Ahl, and oth- were put on conventional regimen alone. Risk factor pro- er APAs were not active. On heat treatment, nuciferine file particularly lipids and left ventricular ejection fraction and lysicamine were degraded into some artifacts which (LVEF) and left ventricular mass (LVM) of each subject 20 exhibited on sedative activity while sanjoinine -A was were assessed before starting indigenous therapy and converted into sanjoinine-Ahl which showed more potent again after three months of therapy. sedative activity. Nuciferine and sanjoinine-A were found [0030] Administration of indigenous drugs resulted in to be major sedative components of native sanjoin, and significant reduction in systolic and diastolic blood pres- that sanjoinine-A and its epimeric artifact, sanjoinine-Ahl sure and elevation in HDL cholesterol was observed at 25 were the active priniples of roasteanjoinine-A and its the end of 3 months in the indigenous drug treated pa- epimeric artifact, sanjoinine-Ahl were the active princi- tients.About 6.7 percentof patients inGroup A developed ples of roasted sanjoin. A scientific basis for heat- fresh ST-T changes as compared to 26.7 percent in the processing (roasting) of this Oriental medicine has been Group B. Significant improvement in LVEF and reduction given. in LVM were also noted." 30 [0034] Reference is made to the publication by Kim, [0031] Reference is made to the publication by Anila, T.H.; Yang, K.S.; Park, J.Y. of the College of Pharmacy, L.; Vijayalakshmi, N.R. of the Department of Biochemis- Sookmyung Women’s University, Seoul 140-742, Korea try, University of Kerala, Kariavattom, Trivandrum 695 titled the Effect of processed Cyperi Rhizoma on rat kid- 581, Kerala, India and titled the Flavonoids from Emblica ney function and published in Yakhak Hoeji. v. 42(1): p. officinalis and Mangifera indica-effectiveness for dyslip- 35 70-74, 1998 which reads as " [] has idemia which appeared in the Journal of Ethnopharma- been used as an analgesic, antiinflammatory agent, di- cology. v. 79(1): p. 81-87, 2002 and reads as Flavonoids uretic and emmenagogue in folk remedies. Cyperi Rhi- from [Emblica officinalis] and [Mangifera indica] effec- zomata, processed and unprocessed, were extracted tively reduce lipid levels in serum and tissues of rats in- with MeOH and fractionated with petroleum ether chlo- duced hyperlipidemia. Hepatic HMG CoA reductase ac- 40 roform, butanol and water. In order to investigate the ef- tivity was significantly inhibited in rats fed [E.officinalis] fects of their fractions on kidney function of acute renal flavonoids. But increase of this enzyme was observed in failure rats induced by HgCl2, urinary volume, BUN, rats administered [M.indica] flavonoids. The degradation (blood urea nitrogen) creatinine, uric acid were deter- and elimination of cholesterol was highly enhanced in mined. The diuretic effect of processed Cyperi Rhizoma both the groups. In [E.officinalis], the mechanism of hy- 45 was significantly increased in renal failure rats, on serum polipidemic action is by the concerted action of inhibition chemical parameters, the significant inhibition of BUN of of synthesis and enhancement of degradation. In the oth- processed Cyperi Rhizoma was revealed. er group [M.indica] inhibition of cholesterogenesis was [0035] Reference is made to the publication by Shar- not encountered but significant degradation of cholester- ma, S.R.; Dwivedi, S.K.; Swarup, D. of the Division of ol was noted, which may be the pivotal factor for hypol- 50 Medicine, Indian Veterinary Research Institute, Izatna- ipidemic activity in this case. gar 243 122, UP, India titled the Hypoglycaemic potential [0032] Though the mechanisms differ in the two cases, of Mangifera indica leaves in rats which appeared in the the net effect is to lower lipid levels." International Journal of Pharmacognosy. v. 35(2): p. [0033] Reference is made to the publication by Han, 130-133, 1997 and which reads thus Hypoglycaemic ac- B.H.; Park, M.H.; Han, Y.N. of the Natural Products Re- 55 tivity of 50 percent ethanol extract of [Mangifera indica] search Institute, Seoul National University, Seoul tender leaves was studied in normal and streptozotocin 110-460, Korea titled the Sedative activity of aporphine induced diabetic rats. In normal rats, the extract was ad- and cyclopetide alkaloids isolated from the seeds of Zizy- ministered only once in doses of 100, 250 and 500 mg/kg

6 9 EP 2 326 338 B1 10 per os. The highest decrease (37.73 percent) in plasma and antiobesity medicine, on obesity and diabetes- glucose levels was obtained with 250 mg dose after 8 h associated cardiac hypertrophy and discuss the role of administration. In diabetic rats, the extract produced of modulation of cardiac angiotensin II type 1 recep- significant antihyperglycaemic effect within 3 days when tor (AT(1)) expression in the effect. METHODS: SOE given at 250 mg/kg/day per os for 10 days. LD50 of the 5 (100 mg/kg) was given orally to male Zucker diabetic extract was above 4.64 gm/kg per os. fatty (ZDF) rats for 7 weeks. At the end-point of the [0036] Reference is made to the publication by Teix- treatment, the hearts and left ventricles were eira, C.C.; Pinto, L.P.; Kessler, F.H.P.; Quadros da Paix- weighed, cardiomyocyte cross-sectional areas were ao, L.; Miura, C.S.; Guimaraes, M.S.; Miura, M.S.; Gast- measured, and cardiac gene profiles were analysed. aldo, G.J.; Fuchs, F.D. of the Departamento de Farma- 10 On the other hand, angiotensin II-stimulated embry- cologia da Universidad Federal do Rio Grade do Sul and onic rat heart-derived H9c2 cells and neonatal rat Hospital de Clinicas de Porto Alegre, CEP 90 050 170 cardiac fibroblasts were pretreated with SOE and Porto Alegre, Brasil titled Is the decoction of mango one of its prominent components mangiferin (MA), leaves an antihyperglycemic tea ? and which appeared respectively. Atrial natriuretic peptide (ANP) mRNA in the Fitoterapia. v. 69(2): p. 165-168, 1998 and reads 15 expression and protein synthesis and [(3)H]thymi- thus " The use of alternative therapies to treat diabetes, dine incorporation were determined. RESULTS: including teas prepared with different plants, is wide- SOE-treated ZDF rats showed less cardiac hyper- spread in Brazil. An ethnopharmacological survey shows trophy (decrease in weights of the hearts and left the prevalent use of a tea prepared with leaves of mango ventricles and reduced cardiomyocyte cross-sec- ([Mangifera indica]) by Brazilian diabetic patients. There- 20 tional areas). SOE treatment suppressed cardiac fore, the claimed hypoglycemic effect of this preparation overexpression of ANP, brain natriuretic peptide has been investigated experimentally in normal rats and (BNP) and AT(1) mRNAs and AT(1) protein in ZDF in streptozotocin-induced diabetic rats, and clinically in rats. SOE (50-100 microg/ml) and MA (25 micromol) healthy volunteers. These results, showing no hypogly- suppressed angiotensin II-induced ANP mRNA cemic effect of the treatment, strongly suggest that man- 25 overexpression and protein synthesis in H9c2 cells. go tea connot be recommended as an antidiabetic treat- They also inhibited angiotensin II-stimulated ment." [(3)H]thymidine incorporation by cardiac fibroblasts. [0037] Reference is made to the publication by Ade- CONCLUSIONS: Our findings demonstrate that ribigbe, A.O.; Emudianughe, T.S.; Lawal, B.A.S. of the SOE decreases cardiac hypertrophy in ZDF rats, at Department of Pharmacology and Therapeutis Universi- 30 least in part by inhibiting cardiac AT(1) overexpres- ty of Ilorin, Nigeria titled Antihyperglycaemic effect of sion. These studies provide insights into a potential Mangifera indica in rat which appeared in the Phytother- cardioprotective role of a traditional herb, which sup- apy Research. v. 13(6): p. 504-507, 1999 and which ports further clinical evaluation in obesity and diabe- reads thus "The effect of the aquoeus extract of [Mangif- tes-associated cardiac hypertrophy. era indica] leaves on blood glucose level was assessed 35 in normoglycaemic, glucose-induced hyperglycaemic b) Toxicology and Applied Pharmacology. 2006 Jan and streptozotocin (STZ)-induced diabetic rats. The 1;210(1-2):78-85Herbal Medicines Research and aqueous extract given orally (1 g/kg) did not alter the Education Centre, Faculty of Pharmacy, TheUniver- blood glucose levels in either normoglycaemic or STZ- sity of Sydney, NSW 2006, Australia. induced diabetic rats. In glucose-induced hyperglycae- 40 Salacia oblonga root improves cardiac lipid metab- mia, however, antidiabetic activity was seen when the olism in Zucker diabetic fatty rats: modulation of car- extract and glucose were administered simultaneously diac PPAR-alpha-mediated transcription of fatty acid and also when the extract was given to the rats 60 min metabolic genes. before the glucose. The hypoglycaemic effect of the Excess cardiac triglyceride accumulation in diabetes aqueous extract of the leaves of [Mangifera indica] has 45 and obesity induces lipotoxicity, which predisposes been attributedto anintestinal reduction of the absorption the myocytes to death. On the other hand, increased of glucose." cardiac fatty acid (FA) oxidation plays a role in the [0038] Reference is made to the following journal cita- development of myocardial dysfunction in diabetes. tions: PPAR-alpha plays an important role in maintaining 50 homeostasis of lipid metabolism. We have previous- a) Diabetes Obesity and Metabolism. 2008 ly demonstrated that the extract from Salacia oblon- Jul;10(7):574-85 ga root (SOE), an Ayurvedic anti-diabetic and anti- Faculty of Pharmacy, University of Sydney, Australia obesity medicine, improves hyperlipidemia in Zucker Salacia oblonga root decreases cardiac hypertrophy diabetic fatty (ZDF) rats (a genetic model of type 2 in Zucker diabetic fatty rats: inhibition of cardiac ex- 55 diabetes and obesity) and possesses PPAR-alpha pression of angiotensin II type 1 receptor. activating properties. Here we demonstrate that AIMS: We investigated the effect of the water extract chronic oral administration of SOE reduces cardiac of Salacia oblonga (SOE), an ayurvedic antidiabetic triglyceride and FA contents and decreases the Oil

7 11 EP 2 326 338 B1 12 red O-stained area in the myocardium of ZDF rats, extract functions as a PPAR-alpha activator, provid- which parallels the effects on plasma triglyceride and ing a potential mechanism for improvement of post- FA levels. Furthermore, the treatment suppressed prandial hyperlipidemia and hepatic steatosis in di- cardiac overexpression of both FA transporter pro- abetes and obesity. tein-1 mRNA and protein in ZDF rats, suggesting 5 inhibition of increased cardiac FA uptake as the basis d) Life Sciences. 2004 Aug for decreased cardiac FA levels. Additionally, the 20;75(14):1735-46Herbal Medicines Research and treatment also inhibited overexpression in ZDF rat Education Center, Faculty of Pharmacy A15, The heart of PPAR-alpha mRNA and protein and carni- University of Sydney, NSW 2006, Australia. tine palmitoyltransferase-1, acyl-CoA oxidase and 10 Salacia oblonga improves cardiac fibrosis and inhib- 5’-AMP-activated protein kinase mRNAs and re- its postprandial hyperglycemia in obese Zucker rats. stored the downregulated acetyl-CoA carboxylase Diabetes has a markedly greater incidence of cardi- mRNA. These results suggest that SOE inhibits car- ovascular disease than the non-diabetic population. diac FA oxidation in ZDF rats. Thus, our findings sug- The heart shows a slowly developing increase in fi- gest that improvement by SOE of excess cardiac 15 brosis in diabetes. Extended cardiac fibrosis results lipid accumulation and increased cardiac FA oxida- in increased myocardial stiffness, causing ventricu- tion in diabetes and obesity occurs by reduction of lar dysfunction and, ultimately, heart failure. Revers- cardiac FA uptake, thereby modulating cardiac al of fibrosis may improve organ function survival. PPAR-alpha-mediated FA metabolic gene transcrip- Postprandial hyperglycemia plays an important role tion. 20 in the development of type 2 diabetes and cardio- vascular complications, and has been proposed as c) Toxicology and Applied Pharmacology 2006 Feb an independent risk factor for cardiovascular diseas- 1;210(3):225-35Herbal Medicines Research and es. Salacia oblonga (S.O.) is traditionally used in the Education Centre, Faculty of Pharmacy, TheUniver- prevention and treatment of diabetes. We investigat- sity of Sydney, NSW 2006, Australia 25 ed the effects of its water extract on cardiac fibrosis Salacia oblonga root improves postprandial hyperl- and hyperglycemia in a genetic model of type 2 di- ipidemia and hepatic steatosis in Zucker diabetic fat- abetes, the obese Zucker rat (OZR). Chronic admin- ty rats: activation of PPAR-alpha. istration of the extract markedly improved interstitial Salacia oblonga (SO) root is an Ayurvedic medicine and perivascular fibrosis in the hearts of the OZR. It with anti-diabetic and anti-obese properties. Perox- 30 also reduced plasma glucose levels in non-fasted isome proliferator-activated receptor (PPAR)-alpha, OZR, whereas it had little effect in the fasted animals, a nuclear receptor, plays an important role in main- suggesting inhibition of postprandial hyperglycemia taining the homeostasis of lipid metabolism. Here, in type 2 diabetic animals, which might play a role in we demonstrate that chronic oral administration of improvement of the cardiac complications of OZR. the water extract from the root of SO to Zucker dia- 35 Furthermore, S.O. markedly suppressed the over- betic fatty (ZDF) rats, a genetic model of type 2 dia- expression of mRNAs encoding transforming growth betes and obesity, lowered plasma triglyceride and factor betas 1 and 3 in the OZR heart, which may be total cholesterol (TC) levels, increased plasma high- an important part of the overall molecular mecha- density lipoprotein levels and reduced the liver con- nisms. S.O. dose-dependently inhibited the increase tents of triglyceride, non-esterified fatty acids (NE- 40 of plasma glucose in sucrose-, but not in glucose- FA) and the ratio of fatty droplets to total tissue. By loaded mice. S.O. demonstrated a strong inhibition contrast, the extract had no effect on plasma triglyc- of alpha-glucosidase activity in vitro, which is sug- eride and TC levels in fasted ZDF rats. After olive oil gested to contribute to the improvement of postpran- administration to ZDF the extract also inhibited the dial hyperglycemia. increase in plasma triglyceride levels. These results 45 suggest that SO extract improves postprandial hy- e) Ahuja, G.L. Journal of the National Integrated perlipidemia and hepatic steatosis in ZDF rats. Ad- Medical Association. v.32(3): p. 9-11, 1990. ditionally, SO treatment enhanced hepatic expres- Role of Ayurvedic drugs-[Terminalia arjuna, Boer- sionof PPAR-alpha mRNAand protein, and carnitine haavia diffusa, Commiphora mukul, Santalum al- palmitoyltransferase-1 and acyl-CoA oxidase mR- 50 bum, Allium sativum, Terminalia chebula, Achyran- NAs in ZDF rats. In vitro, SO extract and its main thes aspera, Nardostachys, Aegle marmelos, component mangiferin activated PPAR-alpha luci- Pirorhiza kurroa], singly or in combination in curing ferase activity in human embryonic kidney 293 cells hypertension, angina, cardiac failure, hypotension and lipoprotein lipase mRNA expression and en- and cholesterolaemia has been discussed zyme activity in THP-1 differentiated macrophages; 55 these effects were completely suppressed by a se- [0039] It has also been reported that the combinations lective PPAR-alpha antagonist MK-886. The find- of extracts of [Curcuma longa] and Phyllanthus Emblica ings from both in vivo and in vitro suggest that SO exhibited good reduction in blood sugar level. Reference

8 13 EP 2 326 338 B1 14 is made to the publication titled "Hypoglycaemic activity Division of Medicine, Indian Veterinary Research Insti- of Curcuma longa Linn. Phyllanthus Emblica Linn. And tute, Izatnagar in their publication titled " the Hypogly- their various extractive combinations on albino rats "by caemic potential of Mangifera indica leaves in rats " Singh, A.K.; Chaudhary, R.; Manohar, S.J. of the College which appeared in the International Journal of Phrama- of Pharmacy, Push Vihar, New Delhi. 5 cognosy. v. 35(2): p. 130-133, 1997 have reported that [0040] In the publication of Rajagopalan, K.; Sasidhar- 50 percent ethanol extract of Mangifera indica tender nan, K. of the Keraleeya Ayurveda Samajam Hospital, leaves significant anti-hyperglycaemic effect within 3 Shoranur, Kerala, titled "The Evaluation of the clinical days management of Prameha Roga (diabetes mellitus) which [0047] Mahapatra, B. of the Dravyaguna, Gopabandhu appeared in the Aryavaidyan. v. 14(1): p. 33-43, 2000 it 10 Ayurveda Mahavidyalaya, Puri in their publication titled has been stated that for the management of diabetes "the hypoglycaemic activity of Coscinium fenestratum mellitus a formulation containing Emblica officinalis, Cur- (Gaertn.) Colebr" which appeared in the Journal of Re- cuma longa, , Cyperus rotundus, search in Ayurveda and Siddha. v. 18(3-4): p. 89-96, Terminalia chebula, Syzygium cumini, Swertia chirata 1997 have reported the significant hypoglycaemic activ- etc can be used 15 ity. [0041] It is also reported in the publication of Bone, K. [0048] In the publication of Ghosh, D.; Uma, R.; The- of the Medicinal Herba Private Limited, PO Box 713, War- jomoorthy, P.; Veluchamy, G. of the Central Research wick 4370, Australia titled " the Turmeric- The spice of Institute (Siddha), Arumbakkam, Madras titled "The Hy- life " and published in the British Journal of Phytotherapy. poglycaemic and toxicity studies of a combination of Em- V. 2(2): p. 51-60, 1991 that curcuma longa can be used 20 blica & T. Chebula " which appeared in the Journal of for lowering cholesterol Research in Ayurveda and Siddha. v. 11(1-4): p. 78-89, [0042] In the publication titled " Biologically active prin- 1990 have reported significant hypoglycaemic activity in ciples isolated from Salacia oblonga Wall" authored by fasting rabbits the drug was found to be non-toxic even Augusti, K.T.; Joseph, P. and Babu, T.D. of Amala Can- when administered in high dose. cer Research Centre, Thrissur 680553, Kerala, which ap- 25 [0049] Puri, D.; Baral, N. of the Department of Bio- peared in the Indian Journal of Physiology and pharma- chemistry, B.P.Koirala Institute of Health Sciences, Dha- cology. V. 39(4): p. 415-417, 1995 discloses that two bi- ran, Nepal in their publication titled " the Hypoglycaemic ologically active fractions have been isolated Salacia ob- effect of [Biophytum sensitivum] in the alloxan diabetic longa by chromatography. The chloroform eluted fraction rabbits " which appeared in the Indian Journal of Physi- by TLC demonstrated hypoglycemic potency of an equal 30 ology and Pharmacology. V. 42(3): p. 401-406, 1998 dose of tolbutamide in albino rats. have reported that that the plant material has significant [0043] In another publication titled Anti-peroxidative antidiabetic effect. and hypoglycaemic activity of extract in diabetic rats au- [0050] In the publication of Mengi, S.A.; Deshpande, thored by Krishnakumar, K.; Augusti, K.T.; Vijayammal, S.G. Of theC.U.S. College of Pharmacy, SNDT Women’s P.L. of the Department of Biochemistry, University of Ker- 35 University, Sir Vithaldas Vidya Vihar, Mumbai titled " An ala, which appeared in pharmaceutical Biology. V. 38(2): Assessment of ocular anti-inflammatory activity of roots p. 101-105, 2000, it has been observed that the root bark and leaves of Butea frondosa : A histopathological study" of the herb possess antidiabetic and antiperoxidative ac- published in British Journal of Phytotherapy. V. 5(2): p. tivities and is useful in the treatment of diabetes and as- 87-88, 1998 have revealed that Butea frondosa, topically sociated renal complications. 40 applied, acted as an anti-inflammatory agent in experi- [0044] Prince, P.S.M.; Menon, V.P.; Pari, L. of the De- mentally induced inflammation of the eye partment of Biochemistry, Annamalai University, An- [0051] Gupta, S.; Sanual, S.N.; Kanwar, U. Of the De- namalai Nagar in their publication titled " Hypoglycaemic partment of Zoology, Punjab University, Chandigarh in activity of Syzygium cumini seeds" which appeared in their publication Titled "Effects of embelin, an antifertility the Journal of Ethnopharmacology. v. 61(1): p. 1-7, 1998 45 agent, on the lipid metabolism of male albino rats "which have observed that Oral administration of the aqueous appeared in the Fitoterapia. v. 60(4): p. 331-338, 1989 extract of the seed for 6 weeks resulted in a significant have observed that a benzoquinone isolated from Em- reduction in blood glucose and an increase in total hae- belia ribes, revealed significant impairment in lipid me- moglobin. tabolism. [0045] In the publication of Jain, A.K.; Shaw, B.P. Re- 50 [0052] Amin, K.M.Y.; Ahmed, S.; Khan, N.A. of the De- search Department, Shree Visudanand Saraswati Mar- partment of Ilmul Advia, A.K. Tibbiya College, AMU Ali- wari Hospital, Calcutta titled " Effect of herbal compound garh in their publication titled "Anti-nephrotic syndrome on maturity onset diabetes " which appeared in the An- ethnic drug Bishiri Booti (Aerva lanata) - Experimental cient Sci. Life. V. 7(1), p. 12-16, 1987 they have reported study of relevant pharmacological actions" presented at the antidiabetes effect of an herbal compound drug con- 55 the Fourth Internat.Cong.Ethnobiol., NBRI, Lucknow. p. sisting of two herbs namely Gymnema sylvestre and 94, 17-21 Nov. 1994 explains that [A. lanata], a wildly Sizygium cumini. growing and cultivable herb of north India is used as a [0046] Sharma, S.R.; Dwivedi, S.K.; Swarup, D. of the folk drug for renal and prostratic ailments. Though not

9 15 EP 2 326 338 B1 16 described in standard texts of Unani Medicine, the drug water. The results obtained showed statistically signifi- is used by some Unani physicians for nephrotic syn- cant reduction in the level of serum cholesterol, serum drome. triglycerides, total lipids, low density lipids, very low den- [0053] In the publication of Khanna, A.K.; Chander, R.; sity lipids. There was a statistically significant increase Kapoor, N.K.; Singh, C.; Srivastava, A.K. Of the Division 5 in the level of high density lipids. However, there was no of Biochemistry, Central Drug Research Institute, Luc- change in the body weight and adipose tissue thickness know titled "Hypolipidemic activity of Terminalia chebula at the level of triceps, nape of neck and abdomen just in rats" which Appeared in the Fitoterapia. V. 64(4): p. below umblicus after therapy. 351-356, 1993 have reported that the hypolipidemic ac- [0058] Reference is made to the publication by Ahir- tion of the ethyl acetate soluble fraction of the alcoholic 10 war, B.; Singhai, A.K.; Dixit, V.K. Of the Department of extract of [T. chebula] stem Pharmaceutical Sciences, Dr.H.S.Gour University, Sa- [0054] In the publication of Amirthaveni, M.; Vijayalak- gar 470 003, MP, India Titled as Effect of Terminalia shmi, P.; Niklia, M.N. of the Department of Family and chebula fruits on lipid profiles of rats And published by Community Science, Avinashilingam University, Coim- Journal of Natural Remedies. v. 3(1): p. 31-35, 2002 batore titled "Lipid profile of the heart patients and healthy 15 Which reads as The ethanolic extract and ethyl acetate volunteers and the effect of supplementation of Kadukkai fractions of [Terminalia chebula] fruits were found to pos- (Terminalia chebula) on hypercholesterolemicsess significant hypolipidaemic activity. The most active patients "published by Indian Journal of Nutrition and Di- extract of [T.chebula] is ethyl acetate fraction of immature etetics. v. 38(3): p. 83-88, 2001 reveals that [Terminalia fruits, which was able to bring high serum lipid to normal chebula] (Kadukkai) has been found to possess cardio 20 level. tonic and hypocholesterolemic effect. [0059] Reference is made to the publication by Ahir- [0055] In the publication by Awasthi, A.K.; Kothari, K.; war, B.; Singhai, A.K.; Dixit, V.K.* Of the Department of Sharma,R.K. ofthe Departmentof Kayachikitsa, Rishikul Pharmaceutical Sciences, Dr. H.S. Gour University, Sa- State Ayurvedic College, Haridwar, UP, in their publica- gar 470 003, Madhya Pradesh, India Titled the Effect of tion titled "Role of Haritakyadi vati in management of sta- 25 Terminalia chebula fruits on lipid profiles of rats And pub- ble angina "Published by Aryavaidyan. v. 9(4): p. lished by Journal of Natural Remedies. v. 3(1): p. 31-35, 214-219, 1996 have reported that Haritakivati (HT) is 2003 Which reads as In atherogenic diet induced hyper- composed of seven herbal drugs such as Terminalia lipidemic model, the rats receiving alcoholic extract of chebula, Acorus calamus, Pluchea lanceolata, Piper immature (IMF), mature (MF) fruits and ethyl acetate sol- longum, Zingiber officinale, Hedychium spicatum and In- 30 uble fraction (immature fruits) of [Terminalia chebula] ula racemosa and when Patients were administered 2 treatment showed marked reduction in total cholesterol tablets of HT orally, the gradation of chest pain was found (TC), total triglyceride (TG), total protein (TP) and eleva- to be shifted towards less severe grades and anginal tion in high density lipoprotein cholesterol (HDL-C). In frequency was reduced. Reductions in serum cholesterol normocholesterolemic model, the feeding of ethanolic and serum triglyceride levels were significant. 35 extract (immature fruits) lowered the levels of TC, TG, [0056] Reference is made to the publication by TP and increased level of HDL-C. The most active extract Awasthi, A.K.; Kothari, K.; Sharma, R.K. Of the Depart- of [T.chebula] is ethyl acetate fraction of immature fruits, ment of Kayachikitsa, Rishikul State Ayurvedic College, which was able to bring high serum lipid to normal level. Haridwar, UP, India Titled Role of Haritakyadi vati in man- [0060] Reference is made to the publication by Mand, agement of stable angina Published by Aryavaidyan. v. 40 J.K.; Soni, G.L.; Gupta, P.P.*; Rattan Sigh of the Depart- 9(4): p. 214-219, 1996 And reads as Haritakivati(HT) is ment of Biochemistry, Punjab Agricultural University, Lu- composed of seven herbal drugs such as [Terminalia dhiana 141 004, Punjab, India titled Effect of Amla (Em- chebula, Acorus calamus, Pluchea lanceolata, Piper blica officinalis) on the development of atherosclerosis longum, Zingiber officinale, Hedychium spicatum] and on hypercholesterolemic rabbits which appeared in the [Inula racemosa]. 20 Patients were administered 2 tab- 45 Journal of Research and Education in Indian Medicine. lets of HT orally, TDS for 2 months and observations v. 10(2): p. 1-7, 1991 and reads thus "Feeding of Amla were made. The gradation of chest pain was found to be to the hypercholesterolemic rabbits for 12 weeks showed shifted towards less severe grades and anginal frequen- a two prong effect, its feeding increased the lipid mobili- cy was reduced. Reduction in serum cholesterol and se- zation and catabolism and retarded the deposition of li- rum triglyceride levels were significant. NSL, New Delhi 50 pids in the extrahepatic tissues. [0057] Reference is made to the publication by Sood, [0061] Feeding of [E.officianalis] initially raised the R.; Sharma, A.K. Of the P.G.Department of Kayachikitsa, plasma lipids and cholesterol levels but by the end of 12 N.I.A., Japipur 302 002, Rajasthan, India Titled Effect of weeks, their levels were reduced significantly below the Bala Haritaki on hypercholesterolaemia And published levels in the control group. Lipid levels of liver were also in Journal of Research in Ayurveda & Siddha. v. 21(1-2): 55 significantly lowered. Though lipid levels of aorta in- p. 11-18, 2000 which reads as Bala Haritaki [Terminalia creased during this period but the increase was much chebula] was given to 15 subjects in the dose of 2 gm, less in Amla fed animals as compared to the control twice a day in powdered form for 6 weeks with luke warm group. The degree of atherosclerosis at the end of 12

10 17 EP 2 326 338 B1 18 weeks of Amla feeding was lower as compared to that in the various herbs individually, in the management of di- the control group." abetes and other separate health conditions such as hy- [0062] Reference is made to the publication by Mathur, per-tension, hyper-cholesterolemia and impaired cardi- R.; Sharma, A.; Dixit, V.P.; Verma, M. of the Department ac, renal or ocular health. But no information is available of Zoology, University of Rajasthan, Jaipur 302004 Ra- 5 in respect of a herbal combination which has a combined jasthan, India titled the Hypolipidaemic effect of fruit juice effect as a health protective, promotive and disease pre- of Emblica officinalis in cholesterolfed rabbits published ventive for diabetics that is safe for long term use and in the Journal of Ethnopharmacology. v. 50(2): p. 61-68, having significant combined medicinal values such as 1996 and whichreads thus "[Emblicaofficinalis] juice was reduction of hyperglycemia, reduction in hypoglycemic administered at a dose of 5 ml/kg body weight per rabbit 10 dependency and improvement in the general health of per day for 60 days. Serum cholesterol, TG, phospholipid diabetics patients along with prevention and manage- and LDL levels were lowered by 82 percent, 66 percent, ment of many of the complications arising from diabetes. 77 percent and 90 percent, respectively. Similarly, the In other words, no prior art knowledge is available where tissue lipid levels showed a significant reduction following the specific combination of various herbs is useful for [E.officinalis] juice administration. Aortic plaques were 15 treating simultaneously diabetes and the associated dis- regressed. [E.officinalis] juice treated rabbits excreted ease conditions such as higher than normal levels of gly- more cholesterol and phospholipids, suggesting that the cosylated hemoglobin, serum creatinine, serum total mode of absorption was affected. [E.officinalis] juice is cholesterol, serum LDL, serum VLDL and serum Triglyc- an effective hypolipidaemic agent and can be used as a erides as well as lower than normal levels of serum HDL pharmaceutical tool in hyperlipidaemic subjects." 20 cholesterol, numbness and pain in the limbs, constipation [0063] Han, B.H.; Park, M.H.; Han, Y.N. of the Natural and disturbed sleep arising as a part of the wrong met- Products Research Institute, Seoul, Korea in their publi- abolic processes of diabetes. cation titled " Activity of aporphine and cyclopetide alka- [0069] The use of plant extracts and derivatives of loids isolated from the seeds of Zizyphus vulgaris var. plants for healing and prevention purposes has been de- spinosus, and the fruits and stem bark of Zizyphus jujuba 25 scribed extensively in traditional and folk medicine liter- var. inermis in mice " which was published in the Yakhak ature. Over the centuries, plants have served as a major Hoeji. v. 37(2): p. 143-148, 1993 have reported the sed- source of medicines for treating and prevention of dis- ative activity of the herb eases of mankind. Although recently the ability for syn- [0064] It is known from the publication of Kim, T.H.; thesis and design of new medicines has provided new Yang, K.S.; Park, J.Y. of the College of Pharmacy, Sook- 30 pathways for the development of therapeutic drugs; how- myung Women’s University, Seoul 140-742, Korea in ever, phytomedicines derived from plants still hold a their publication titled "The Effect of processed Cyperi strong position. Rhizoma on rat kidney function " published in Yakhak Hoeji. v. 42(1): p. 70-74, 1998 which reads as [Cyperus Object of the invention rotundus] that the herb has been used as an analgesic, 35 anti-inflammatory agent, diuretic and emmenagogue in [0070] The main object of the invention is to provide a folk remedies. safe and effective herbal formulation and a process for [0065] In the publication of Chatterjee, T.K.;preparing the same, which prevents and treats diabetes Chakraborty, A.; Pathak, M. Of the Pharmacology Re- and associated complications of diabetes. search Laboratory, Department of Pharmaceutical Tech- 40 [0071] Another object of the present invention is to pro- nology, Jadavpur University, Calcutta titled as "Effects vide asafe and effective herbal formulation anda process of plant extract Centella asiatica (Linn.) On cold restraint for preparing the same, which improves the renal function stress ulcer in rats" published by Indian Journal of Ex- and health of the diabetics, reduces the elevated levels perimental Biology. v. 30(10): p. 889-891, 1992 reveals of serum creatinine, decreases the incidence of urinary that the Extract of [C.asiatica] inhibited significantly gas- 45 tract infections and offers better quality of life to the dia- tric ulceration induced by cold and restraint stress (CRS) betic patients in rats. [0072] Yet another object of the invention is to provide [0066] JP2006056836 discloses the anti-diabetic ef- a safe and effective herbal formulation and a process for fect of fruits of Emblica officinale. Plant Foods for Human preparing the same, which prevent the damages to the Nutrition 57, 41-52 (2002) by Arun & Nalini discloses the 50 ophthalmic blood vessels and also prevents and treat- blood sugar reducing effect of Curcuma longa tumeric ments retinopathy associated with diabetes. rhizomes in diabetic albino rats. [0073] Another object of the present invention is to pro- [0067] Medicinal &Aromatic Plants Abstractsby Murali vide a safe and effective herbal composition and a proc- et al., published on 01-03-2005 discloses the antihyper- ess for preparing the same, which improves the cardio- ghycemic effect of a water extract of dry fruits of Femi- 55 vascular health of diabetic patient and reduces hyperten- nalia chebula in experimental diabetes mellitus. sion, improves the ratio of the serum lipid profile and im- [0068] The prior arts described above, indicate that proves cardiac functional parameters of a diabetic pa- some studies have been carried out into effectiveness of tient.

11 19 EP 2 326 338 B1 20

[0074] Still another object of the present invention is of the Combretaceae family, to provide a safe and effective herbal formulation and a n) The Species Centella asiatica (L.) Urban of the process for preparing the same, which reduces the pain Apiaceae family and / or the Species Strychnos nux- and numbness associated with peripheral neuropathy, vomica L. (Synonym: Strychnos ligustrina Blume) of improves wound healing of diabetic ulcers , improves 5 the Strychnaceae family, and / or the Species Butea bowel evacuation and sleep and generally improves the frondosa Koen. ex Roxb. (synonym: Butea mono- quality of life of the diabetic patient. sperma (Lam.)Taub. of thePapilionaceae family and [0075] Yet another objective of the present invention /or the Species Acacia catechu (L.f.) Willd. of the is to provide a safe and effective herbal formulation which Mimosaceae family, is processed as a synergestic herbal compound powder 10 o) The Species Coscinium fenestratum (Gaertn.) or fermented herbal nutraceutical beverage or high-fiber Colebr. of the family and / or the nutraceutical food stuff(s) or extract /concentrate which Species of herbs of the Genus of the Ber- is further formulated using known conventional process- beridaceae family, and es to tablets or capsules or granules or syrups or herbal p) The species of herbs of the Genus Zizyphus of health drink or inhalable herbal medicinal preparations 15 the Rhamnaceae family. or ocular preparations or transdermal absorbable prep- arations such as ointments / gels or injectable medicine. [0077] The preffered species of herbs to be used In occasions of the extract / concentrate being further as ingredients in the formulation for the treatment formulated, the formulation may also optionally contain and prevention of diabetes and associated compli- suitable digestive, flavoring, binding, sweetening and ex- 20 cations are: ciepient and / or absorptive adjuvants which are normally used in such formulations, as per the particular require- a)Emblica officinalisGaertn. (Synonym: Phyllanthus ments. emblica L.) of the Euphorbiaceae Family, b) Salacia oblonga Wall. ex Wight & Arn. of the of Summary of the invention 25 the Celastraceae family, c) Strychnos potatorum L. f. of the Strychnaceae [0076] The ingredient herbs of the herbal formula- family, tion for the treatment and prevention of diabetes and d) Vetiveria zizanioides (L.) Nash (Synonym: Andro- other associated complications are: pogon squarrosus Hook f. (non L. f.) of the Poaceae 30 family, a) The Species Emblica officinalis Gaertn. (Syno- e) Curcuma longa L. of the Zingiberaceae family, nym: Phyllanthus emblica L.) of the Euphorbiaceae f) Aerva lanata Juss of the Amaranthaceae family, Family, g) Biophytum sensitivum (L.) DC. (Synonym: Oxalis b) The Species of herbs of the Genus Salacia of the sensitivum L.) of the Oxalidaceae family, of the Celastraceae family, 35 h) Syzygium cumini (L.) Skeels (Synonym: Eugenia c) The Species Strychnos potatorum L. f. of the jambolana Lam.) of the Myrtaceae family Strychnaceae family, i) Mangifera indica L. of the Anacardiaceae family, d) The Species Vetiveria zizanioides (L.) Nash (Syn- j) peltata (Lam..) Hook. f. & Thoms. of the onym: Andropogon squarrosus Hook f. (non L. f.) of Menispermaceae family, the Poaceae family, 40 k) Embelia ribes Burm. f. of the Myrsinaceae family, e) The Species Curcuma longa L. of the Zingiber- l) Cyperus rotundus L., (Synonym: Cyperus rotundus aceae family, L. ssp. tuberosus (Rottb.) Kuekenth; and Cyperus f) The Species of herbs of the Genus Aerva of the tuberosus Rottb.) of the Cyperaceae family, Amaranthaceae family, m) Terminalia chebula (Gaertn.) Retz. of the Com- g) The Species of herbs of the Genus Biophytum of 45 bretaceae family, the Oxalidaceae family, n) Centella asiatica (L.) Urban of the Apiaceae family h) The Species of herbs of the Genus Syzygium of o) Coscinium fenestratum (Gaertn.) Colebr. of the the Myrtaceae family Menispermaceae family, and i) The Species Mangifera indica L. of the Anacar- p) Zizyphus jujuba Lamk. (Synonym: Zizyphus mau- diaceae family, 50 ritiana Lamk.) of the Rhamnaceae family. j) The Species of herbs of the Genus Cyclea and /or the the Genus Cissampelos of the Menispermaceae [0078] Any one or any few or all parts of the above family, plants, processed in any form may be used in the k) The Species of herbs of the Genus Embelia of the formulation, with varying degrees of effectiveness. Myrsinaceae family, 55 The formulation shall give the most desired and op- l) The Species of herbs of the Genus Cyperus of the timum results of clinical efficacy and safety, when Cyperaceae family, the following parts of the preferred ingredient plants m) The Species Terminalia chebula (Gaertn.) Retz. are used:

12 21 EP 2 326 338 B1 22

a) Fruits without the seeds of Emblica officinalis Am are collected and washed in water to remove Gaertn. (Synonym: Phyllanthus emblica L.) of the external impurities. The they are cut into longitudinal Euphorbiaceae Family, pieces of 1 to 1.5 inches length and again washed b) Roots of Salacia oblonga Wall. ex Wight & Arn. well with water. The clean pieces are dried in mild of the of the Celastraceae family, 5 direct sunlight and then further cut into smaller piec- c) Seeds of Strychnos potatorum L. f. of the es of 1 to 1.5 centimeters length. These pieces are Strychnaceae family, pulverized using mesh size of 5 millimeter, first and d) Fibrous roots of Vetiveria zizanioides (L.) Nash then using 3 millimeter, after that, to yield a homog- (Synonym: Andropogon squarrosus Hook f. (non L. enous powder of average particle size of 1 millimeter f.) of the Poaceae family, 10 to 3 millimeters. e) Rhizomes of Curcuma longa L. of the Zingiber- aceae family, c) Strychnos potatorum L. f. : Dried and dispersible f) Whole plant of Aerva lanata Juss of the Amaran- seeds of Strychnos potatorum L. f are collected and thaceae family, washed well for clearing the physical impurities. The g) Whole plant of Biophytum sensitivum (L.) DC.15 seeds are then dried in good sunlight and further (Synonym: Oxalis sensitivum L.) of the Oxalidaceae fried in dry heat in a shallow bottom iron frying pan family, at around 60 to 75 degree Celsius. The fried seeds h) Seeds of Syzygium cumini (L.) Skeels (Synonym: are pulverized using 5 millimeter mesh size and fur- Eugenia jambolana Lam.) of the Myrtaceae family ther 3 millimeter mesh size to yield a homogenous i) Seed kernels of Mangifera indica L. of the Anac- 20 powder of average particle size of 1 millimeter to 3 ardiaceae family, millimeters. j) Tuberous roots of (Lam..) Hook. f. & Thoms. of the Menispermaceae family, d) Vetiveria zizanioides (L): The fibrous roots of k) Fruits / Seeds of Embelia ribes Burm. f. of the freshly unearthed Vetiveria zizanioides (L) plants are Myrsinaceae family, 25 cut off from the shoot, leaving a gap of 1.5 to 2 cen- l) Rhizomes of Cyperus rotundus L., (Synonym: Cy- timeters. The roots are then washed off the sand and perus rotundus L. ssp. tuberosus (Rottb.) Kuekenth; other physical impurities using water and dried in and Cyperus tuberosus Rottb.) of the Cyperaceae shade and low humidity. The roots when semi dried family, are further cut into smaller pieces of not more than m) Fruits without seeds of Terminalia chebula (Gaer- 30 2 centimeters long. The cut roots are further dried tn.) Retz. of the Combretaceae family, fully and pulverized using 3 millimeter mesh size to n) Whole plant of Centella asiatica (L.) Urban of the yield a homogenous powder of average particle size Apiaceae family of 1 millimeter to 3 millimeters. o) Stem with bark of Coscinium fenestratum (Gaer- tn.) Colebr. of the Menispermaceae family, and 35 e) Curcuma longa L..: The rhizomes of Curcuma lon- p) Fruits with seeds and stem bark of Zizyphus jujuba ga L. are collected and washed off the physical im- Lamk. (Synonym: Zizyphus mauritiana Lamk.) of the purities with boiling water and dried under shade. Rhamnaceae family. The dried rhizomes are as such fed into the pulver- iser with a 5 millimeter mesh size and further a 3 [0079] Preparation of preferred parts of the herbal 40 millimeter mesh size to yield a homogenous powder raw materials for herbal formulation for the treatment of average particle size of 1 millimeter to 3 millime- and prevention of diabetes and associated compli- ters. cations are: f) Aerva lanata Juss.: The whole herb of Aerva lanata a) Emblica officinalis Gaertn : Fresh fruits of Emblica 45 Juss are collected including the root and shoot sys- officinalis Gaertn are collected and cleaned well with tem completely. The plant is washed and cut into water to remove any impurities. The fruits are then pieces of 1.5 to 2 centimeters length. The cut plant wiped dry and cut to two pieces, longitudinally, to the parts are further dried fully in shade and pulverized point of attachment of the fruit stalk. The seeds are using 3 millimeter mesh size to yield a hom ogenous removedand thefruit pulp isdried so as not to expose 50 powder of average particle size of 1 millimeter to 3 the fruit pulp to direct sun - light. The dried fruit pulp millimeters. is powdered in pulverizes of mesh size between 5 millimeters and then and 3 millimeters, to get a ho- g) Biophytum sensitivum (L) DC.: The whole herb of mogenous powder of average particle size of 1 mil- Biophytum sensitivum (L) DC., are collected includ- limeter to 3 millimeters. 55 ing the root and shoot system completely. The plant is washed and cut into pieces of 1.5 to 2 centimeters b) Salacia oblonga Wall. Ex Wight & Am. : Fresh length. The cut plant parts are further dried fully in roots of the plant Salacia oblonga Wall. Ex Wight & shade and pulverized using 3 millimeter mesh size

13 23 EP 2 326 338 B1 24 to yield a homogenous powder of average particle moisture of washing and then the rhizomes are cut size of 1 millimeter to 3 millimeters. into 2 pieces to expose the raw white cut surface. The rhizomes are then further dried in shade to re- h) Syzygium cumini (L) Skeels: Fresh ripe fruits of move maximum moisture from them and then are Syzygium cumini (L) Skeels are collected and the 5 pulverized using 3 millimeter mesh size to yield a fruit pulp is scraped of with rough cloth to leave the homogenous powder of average particle size of 1 seeds completely exposed. The seeds are further millimeter to 3 millimeters. kept in warm water of 40 to 45 degree Celsius for 10 minutes and then it is further wiped dried to remove m) Terminalia chebula (Gaertn.) Retz.: Fresh fruits all traces of water and any adhering fruit pulp. The 10 of Terminalia chebula (Gaertn.) Retz are collected seed is further dried in shade and pulverized using and cleaned well with water to remove any impuri- 3 millimeter mesh size to yield a homogenous pow- ties. The fruits are then wiped dry and cut to two der of average particle size of 1 millimeter to 3 mil- pieces, longitudinally, to the point of attachment of limeters. the fruit stalk. The seeds are removed and the fruit 15 pulp is dried so as not to expose the fruit pulp to i) Mangifera indica L.: Fresh ripe fruits of Mangifera direct sun - light. The dried fruit pulp is powdered in indica L are collected and the seeds are cleaned off pulverizers of mesh size between 5 millimeters and the fruit pulp. The seeds are further dried well in good then and 3 millimeters, to get a homogenous powder sunlight. The dried seeds are cut into two using very of average particle size of 1 millimeter to 3 millime- sharp pliers and the seed coat and seed kernel are 20 ters. separated. The seed coats are discarded and seed kernels are further dried in direct sunlight and the n) Centella asiatica (L) Urban.: The whole herb of kernel are pulverized using 3 millimeter mesh size Centella asiatica (L) Urban, are collected including to yield a homogenous powder of average particle the root and shoot system completely. The plant is size of 1 millimeter to 3 millimeters. 25 washed and cut into pieces of 1.5 to 2 centimeters length. The cut plant parts are further dried fully in j) Cyclea peltata (Lamk.) Hook. f & Thoms.: The fresh shade and pulverized using 3 millimeter mesh size tuberous roots of Cyclea peltata (Lamk.) Hook. f & to yield a homogenous powder of average particle Thoms are collected giving care not to lose any of size of 1 millimeter to 3 millimeters. the long running roots, left in the soil. The roots are 30 then washed well with water to remove physical im- o) Coscinium fenestratum (Gaertn.) Colebr.: The purities and dried in direct sunlight. The dried tuber- stem of Coscinium fenestratum (Gaertn.) Colebr are ous roots are then cut into small pieces of 1.5 to 2 cut from a branch which has more than 3 months of centimeters length and further dried in direct sun- growth. Care is taken to retrieve the entire length of light. These small pieces of Cyclea peltata (Lamk.) 35 the stem so as to minimize the eco-system impact Hook. f & Thoms roots are pulverized using 3 millim- per kilogram of the raw material used. The stem is eter mesh size to yield a homogenous powder of washed well with water, taking precaution ,not to average particle size of 1 millimeter to 3 millimeters. shear of any bark , and dried in direct sunlight. The dried stem is then cut cross sectional, so that each k) Embelia ribes Burm. f: The ripe berries of Embelia 40 cylindrical piece of stem is 1.5 to 2 centimeter long. ribes Burm. f are collected and hand picked to sort The stem pieces are further dried in shade and are out the physical impurities. The rest of the berries fed into the pulveriser with a 5 millimeter mesh size are washed well to further clean them and then dried and further a 3 millimeter mesh size to yield a ho- in direct sunlight after spreading the berries into a mogenous powder of average particle size of 1 mil- thin layer. The well dried berries are then pulverized 45 limeter to 3 millimeters. using 3 millimeter mesh size to yield a homogenous powder of average particle size of 1 millimeter to 3 p) Fruits with seeds and stem bark of Zizyphus jujuba millimeters. Lamk.: Fresh fruits of Zizyphus jujuba Lamk are col- lected and cleaned well with water to remove any l) Cyperus rotundus L.: The fresh rhizomes of Cype- 50 impurities. The fruits are then wiped dry and dried in rus rotundus L are collected and the rhizomes are direct sun - light. The dried fruits are then powdered cut off from the base of the shoot 0.25 to 0.5 centim- in pulverizers of mesh size between 5 millimeters eters and washed well in water to remove all physical and then and 3 millimeters, to get a homogenous impurities. Care must be taken to use water jet with powder of average particle size of 1 millimeter to 3 pressure to remove all the soil particles which usually 55 millimeters. The stem bark of Zizyphus jujuba Lamk gets entangled in the rootlets and root hairs which are sheared off so as not to remove the entire cross arise from the rhizomes. The washed rhizomes are section of the bark which might cause the plant to then dried direct sun light for a day to remove the whither. The sheared bark are cleaned with water

14 25 EP 2 326 338 B1 26

and dried in indirect sunlight. Further it is cut into b) Roots of Species of herbs of the Genus Salacia pieces of 1.5 centimeter to 2 centimeter and further of the of the Celastraceae family , 10 to 15% by w /w; dried in shade. The dried pieces of stem bark and c) Seeds of the Species Strychnos potatorum L. f. then fed into pulverizers of mesh size 3 millimeters, of the Strychnaceae family, 5 to 8% by w /w; to get a homogenous powder of average particle size 5 d) Roots of the Species Vetiveria zizanioides (L.) of 1 millimeter to 3 millimeters Nash (Synonym: Andropogon squarrosus Hook f. (non L. f.) of the Poaceae family, 1 to 5% by w /w; [0080] Whileusing therespective substitutes to the e) Rhizomes of the Species Curcuma longa L. of the preffered herbal ingredients, the corresponding Zingiberaceae family, 5 to 8% by w /w; parts of the substitute plants may be used and pre- 10 f) Wholeplant ofSpecies ofherbs of the Genus Aerva pared in exactly the same way as the original ingre- of the Amaranthaceae family, 5 to 8% by w /w; dients except in three cases, which are as explained g) Whole plant of Species of herbs of the Genus Bi- below: ophytum of the Oxalidaceae family, 1 to 5% by w /w; h) Seeds of Species of herbs of the Genus Syzygium i. When Centella asiatica (L) Urban is being substi- 15 of the Myrtaceae family, 5 to 8% by w /w; tuted with Strychnos nuxvomica L: Leaves of Strych- i) Seeds kernels of the Species Mangifera indica L. nos nuxvomica L is the most preferred part to be of the Anacardiaceae family, 1 to 5% by w /w; used for substitution. Fresh leaves of Strychnos nux- j) Tuberous roots of Species of herbs of the Genus vomica L are collected, washed in water to remove Cyclea and /or roots of the Genus Cissampelos of physical impurities. The leaves are cut into pieces 20 the Menispermaceae family, 1 to 5% by w /w; of 1.5 centimeters to 2 centimeters and then dried k) Seeds of Species of herbs of the Genus Embelia under shade. The dried leaves are then pulverized of the Myrsinaceae family, 1 to 5% by w /w; using 3 millimeter mesh size to yield a homogenous l) Rhizomes of Species of herbs of the Genus Cype- powder of average particle size of 1 millimeter to 3 rus of the Cyperaceae family, 1 to 5% by w /w; millimeters. 25 m) Fruits without seeds of the Species Terminalia chebula (Gaertn.) Retz. of the Combretaceae family, ii. Further, when Centella asiatica (L) Urban is being 15 to 30% by w /w; substituted with Butea frondosa Koen. Ex Roxb: n) Whole plant of the Species Centella asiatica (L.) Flowers of Butea frondosa Koen. Ex Roxb are the Urban of the Apiaceae family and / or leaves of the most preferred part to be used for substitution. Fresh 30 Species Strychnos nux-vomica L. (Synonym: flowers of Butea frondosa Koen. Ex Roxb are col- Strychnos ligustrina Blume) of the Strychnaceae lected, washed in water to remove physical impuri- family, and / or flowers of the Species Butea frondosa ties. The flowers are cut into pieces of 1.5 centime- Koen. ex Roxb. (synonym: Butea monosperma ters to 2 centimeters and then dried under shade. (Lam.) Taub. of the Papilionaceae family and /or The dried flowers are then pulverized using 3 millim- 35 heart wood of the Species Acacia catechu (L.f.) eter mesh size to yield a homogenous powder of Willd. of the Mimosaceae family, 1 to 5% by w /w; average particle size of 1 millimeter to 3 millimeters. o) Stem with bark of the Species Coscinium fenes- tratum (Gaertn.) Colebr. of the Menispermaceae iii. And again when Centella asiatica (L) Urban is family and / or stem with bark of Species of herbs of being substituted with Acacia catechu (L.f) Willd: 40 the Genus Berberis of the family, 5 Heart wood of Acacia catechu (L.f) W illd is the most to 8% w/w and preferred part to be used for substitution. Heart wood p) Fruits with seeds and stem bark of Species of of Acacia catechu (L.f) Willd are collected, washed herbs of the Genus Zizyphus of the Rhamnaceae in water to remove physical impurities. The heart family, 1 to 5% by w /w, wood are then cut into pieces of 1.5 centimeters to 45 2 centimeters and then dried under direct sunlight.. [0082] Wherein the ingredients are powdered to 1 mil- The dried wood is fed into the pulveriser with a 5 limeter to 3 millimeter particle size and blended in a blend- millimeter mesh size and further a 3 millimeter mesh er at 30 to 60 rotations per minutes to obtain the homog- size to yield a homogenous powder of average par- enous herbal formulation. ticle size of 1 millimeter to 3 millimeters. 50 [0083] A preffered embodiment of the present in- vetnion for prevention and treatment of the diabetes [0081] An embodiment of the present invention for and associated complications comprises: prevention and treatment of the diabetes and asso- ciated complications comprises: a) Fruits without seeds of Emblica officinalis Gaertn. 55 (Synonym: Phyllanthus emblica L.) of the Euphor- a) Fruits without seeds of the Species Emblica offic- biaceae Family, 5 to 8% by w /w inalis Gaertn. (Synonym: Phyllanthus emblica L.) of b) Roots of Salacia oblonga Wall. ex Wight & Am. of the Euphorbiaceae Family, 5 to 8% by w /w; the of the Celastraceae family, 10 to 15% by w /w

15 27 EP 2 326 338 B1 28

c) Seeds of Strychnos potatorum L. f. of thewound healing for diabetics. Thus the use of the above Strychnaceae family, , 5 to 8% by w /w; composition improves the chances of wound healing as d) Roots of Vetiveria zizanioides (L.) Nash (Syno- evidenced by reduced time in complete healing of dia- nym: Andropogon squarrosus Hook f. (non L. f.) of betic ulcers. The above formulation also offers the benefit the Poaceae family, 1 to 5% by w /w 5 of improved ocular health for diabetics as evidenced by e) Rhizomes of Curcuma longa L. of the Zingiber- reduction in the incidence of diabetes related retinal cap- aceae family, 5 to 8% by w /w illary bleedings and slowing down in the progress of di- f) Whole plant of Aerva lanata Juss of the Amaran- abetic retinopathy and cataract. It also offers the addi- thaceae family, 5 to 8% by w/w tional benefit of better dermal health for diabetics and g) Whole plant of Biophytum sensitivum (L.) DC.10 management of skin ailments of diabetics as evidenced (Synonym: Oxalis sensitivum L.) of the Oxalidaceae by faster resolving of boils, carbuncles etc which occur family, 1 to 5% by w /w very often in diabetics. Further it offers better quality of h) Seeds of Syzygium cumini (L.) Skeels (Synonym: sleep as evidenced by improvement in sleep patterns of Eugenia jambolana Lam.) of the Myrtaceae family, diabetics previously recorded as having disturbed sleep. 5 to 8% by w /w; 15 Furthermore the formulation has the additional benefit of i) Seeds kernels of Mangifera indica L. of the Anac- reducing the size of the prostrate gland in male diabetics ardiaceae family, 1 to 5% by w /w; suffering from benign prostratic hypertrophy. This formu- j) Tuberous roots of Cyclea peltata (Lam..) Hook. f. lation also offers an equally good or significantly better & Thoms. of the Menispermaceae family, 1 to 5% by option of control for people with identified pre-diabetic w /w; 20 conditions and newly identified diabetics when compared k) Seeds of Embelia ribes Burm. f. of the Myrsinace- with diet and exercise alone or also as an adjuvant to ae family, 1 to 5% by w /w diet and exercise. The composition also acts as an ex- l) Rhizomes of Cyperus rotundus L., (Synonym: Cy- cellent adjuvant with other hypoglycemic drugs and helps perus rotundus L. ssp. tuberosus (Rottb.) Kuekenth; to reduce their dose. and Cyperus tuberosus Rottb.) of the Cyperaceae 25 [0086] The main advantage of the above invention is family, 1 to 5% by w /w that it provides safe and effective herbal formulation m) Fruits without seeds of Terminalia chebula (Gaer- which simultaneously prevents oxidative damage to tn.) Retz. of the Combretaceae family, 15 to 30% by heart and its blood vessels and also reduces hyperten- w /w sion. According to another embodiment of the present n) Whole plant of Centella asiatica (L.) Urban of the 30 invention, the formulations described in any of the pre- Apiaceae family, 1 to 5% by w /w ceeding embodiments are processed as an extract /con- o) Stem with bark of Coscinium fenestratum (Gaer- centrate. tn.) Colebr. of the Menispermaceae family, 5 to 8% [0087] Still in another embodiment of the present in- w/w, and vention, the formulations described in any of the preceed- p) Fruits with seeds and stem bark of Zizyphus jujuba 35 ing embodiments are processed as an extract / concen- Lamk. (Synonym: Zizyphus mauritiana Lamk.) of the trate and further formulated using known conventional Rhamnaceae family, 1 to 5% by w /w processes in the form of capsules or tablets or syrups or eye drops or dermal patches or nasal sprays or injectable [0084] Wherein the ingredients are powdered to 1 mil- medicine or ointments or gels absorbable through skin. limeter to3 millimeterparticle size and blended ina blend- 40 [0088] In yet another embodiment of the present in- er at 30 to 60 rotations per minutes to obtain the homog- vention, the formulations described in any of the preceed- enous herbal formulation. ing embodiments is processed as extract / concentrate [0085] The above mentioned formulation reduces lev- and is further formulated using known conventional proc- els of blood sugar as evidenced by before and after Fast- esses to appropriate pharmacological formlations, suit- ing and Post-prandial Blood readings and also reduces 45 able digestive, flavoring, exciepient and / or absorptive the glycosylation of hemoglobin as evidenced by before pharmacological adjuvants, which are normally used in and after HB1AC values. The above formulation also re- such formulations, as per the specific requirements are duces Total cholesterol, LDL Cholesterol and Serum added. Triglycrides in before and after trials and at the same time [0089] Thus the composition of the present invention it increases the HDL cholesterol. The above formulation 50 is not a mere mixture of the ingredients used resulting in additionally offers improved cardiovascular health for di- aggregation of their properties but a mixture having syn- abetics simultaneously suffering from cardio vascular ergistically enhanced properties useful in prevention of diseases as evidenced by reduction of hypertension and oxidative damage to heart and its blood vessels and improved exercise tolerance. It also reduces serum cre- which reduces hypertension. atinine and also improves the quality of life of the diabetic 55 [0090] The inventions are described with reference to as evidenced by reduction in pain and numbness, im- the examples, which are provided by way of illustration provedsleep and improved bowelevacuation. The above only, and these examples should not be construed to limit formulation also offers the additional benefit of improved the scope of the present invention:

16 29 EP 2 326 338 B1 30

Examples of process for preparation of herbal for- zizanioides (L.) Nash (Synonym: Andropogon squarro- mulationfor prevention and treatment of the diabetes sus Hook f. (non L. f.) of the Poaceae family, 40 grams, and associated complications: Rhizomes of Curcuma longa L. of the Zingiberaceae fam- ily, 80 grams, Whole plant of Aerva lanata Juss of the Example 1: 5 Amaranthaceae family, 80 grams, Whole plant of Bio- phytum sensitivum (L.) DC. (Synonym: Oxalis sensitivum [0091] As per this Example, one kilogram of the formu- L.) of the Oxalidaceae family, 40 grams, Seeds of Syzy- lation is made by using Fruits without seeds of Emblica gium cumini (L.) Skeels (Synonym: Eugenia jambolana officinalis Gaertn. (Synonym: Phyllanthus emblica L.) of Lam.) of the Myrtaceae family, 80 grams; Seeds kernels the Euphorbiaceae Family, 80 grams, Roots of Salacia 10 of Mangifera indica L. of the Anacardiaceae family, 50 oblonga Wall. ex Wight & Am. of the of the Celastraceae grams, Tuberous roots of Cyclea peltata (Lam..) Hook. family, 100 grams, Seeds of Strychnos potatorum L. f. of f. & Thoms. of the Menispermaceae family, 50 grams; the Strychnaceae family, 80 grams; Roots of Vetiveria Seeds of Embelia ribes Burm. f. of the Myrsinaceae fam- zizanioides (L.) Nash (Synonym: Andropogon squarro- ily, 15 grams, Rhizomes of Cyperus rotundus L., (Syno- sus Hook f. (non L. f.) of the Poaceae family, 50 grams, 15 nym: Cyperus rotundus L. ssp. tuberosus (Rottb.) Rhizomes of Curcuma longa L. of the Zingiberaceae fam- Kuekenth; and Cyperus tuberosus Rottb.) of the Cyper- ily, 80 grams, Whole plant of Aerva lanata Juss of the aceae family, 50 grams, Fruits without seeds of Termi- Amaranthaceae family, 80 grams, Whole plant of Bio- nalia chebula (Gaertn.) Retz. of the Combretaceae fam- phytum sensitivum (L.) DC. (Synonym: Oxalis sensitivum ily, 150grams, Whole plant of Centellaasiatica (L.) Urban L.) of the Oxalidaceae family, 50 grams, Seeds of Syzy- 20 of the Apiaceae family, 10 grams, Stem with bark of Co- gium cumini (L.) Skeels (Synonym: Eugenia jambolana scinium fenestratum (Gaertn.) Colebr. of the Menisper- Lam.) of the Myrtaceae family, 80 grams; Seeds kernels maceae family, 50 grams, and Fruits with seeds of Zizy- of Mangifera indica L. of the Anacardiaceae family, 50 phus jujuba Lamk. (Synonym: Zizyphus mauritiana grams, Tuberous roots of Cyclea peltata (Lam..) Hook. Lamk.) of the Rhamnaceae family, 25 grams. f. & Thoms. of the Menispermaceae family, 50 grams; 25 [0094] The specified parts of the above mentioned Seeds of Embelia ribes Burm. f. of the Myrsinaceae fam- herbs were taken in the above mentioned proportion and ily, 15 grams, Rhizomes of Cyperus rotundus L., (Syno- powdered. The powders were mixed to get the formula- nym: Cyperus rotundus L. ssp. tuberosus (Rottb.) tion. The formulation prepared as described above is dis- Kuekenth; and Cyperus tuberosus Rottb.) of the Cyper- pensed as sachets containing 6 grams in each sachet. aceae family, 50 grams, Fruits without seeds of Termi- 30 When used the content of the sachet is to be added to nalia chebula (Gaertn.) Retz. of the Combretaceae fam- one and half to two liters of water in a suitable vessel and ily, 150 grams, Whole plant of Centella asiatica (L.) Urban boiled for two minutes. Then the powdered composition of the Apiaceae family, 10 grams, Stem with bark of Co- is to be strained and removed from the vessel to be dis- scinium fenestratum (Gaertn.) Colebr. of the Menisper- pensed off. The water so made is to be completely used maceae family, 50 grams, and Fruits with seeds of Zizy- 35 up by the diabetic patient in twenty four hours, in 8 or 6 phus jujuba Lamk. (Synonym: Zizyphus mauritiana divided doses. Lamk.) of the Rhamnaceae family, 25 grams. [0092] The herbs are taken in the above proportion and Example 3: powdered. The powders are mixed to get the composition of the Example 1. The composition prepared as de-40 [0095] As per this Example, one kilogram of the formu- scribed above is dispensed as sachets containing 6 lation is made by using Fruits without seeds of Emblica grams in it. The content of the sachet is to be added to officinalis Gaertn. (Synonym: Phyllanthus emblica L.) of one and half to two liters of water in a suitable vessel and the Euphorbiaceae Family, 80 grams, Roots of Salacia boiled for two minutes. Then the powdered composition oblonga Wall. ex Wight & Arn. of the of the Celastraceae is to be strained and removed from the vessel to be dis- 45 family, 100 grams, Seeds of Strychnos potatorum L. f. of pensed off. The water so made is to be completely used the Strychnaceae family, 80 grams; Roots of Vetiveria up by the diabetic patient in twenty four hours, using it zizanioides (L.) Nash (Synonym: Andropogon squarro- instead of drinking water, in 8 or 6 divided doses. sus Hook f. (non L. f.) of the Poaceae family, 40 grams, Rhizomes of Curcuma longa L. of the Zingiberaceae fam- Example 2: 50 ily, 80 grams, Whole plant of Aerva lanata Juss of the Amaranthaceae family, 80 grams, Whole plant of Bio- [0093] As per this Example, one kilogram of the formu- phytum sensitivum (L.) DC. (Synonym: Oxalis sensitivum lation is made by using Fruits without seeds of Emblica L.) of the Oxalidaceae family, 40 grams, Seeds of Syzy- officinalis Gaertn. (Synonym: Phyllanthus emblica L.) of gium cumini (L.) Skeels (Synonym: Eugenia jambolana the Euphorbiaceae Family, 100 grams, Roots of Salacia 55 Lam.) of the Myrtaceae family, 80 grams; Seeds kernels oblonga Wall. ex Wight & Arn. of the of the Celastraceae of Mangifera indica L. of the Anacardiaceae family, 50 family, 100 grams, Seeds of Strychnos potatorum L. f. of grams,Tuberous roots of Cyclea peltata (Lam..) Hook. f. the Strychnaceae family, 80 grams; Roots of Vetiveria & Thoms. of the Menispermaceae family, 50 grams;

17 31 EP 2 326 338 B1 32

Seeds of Embelia ribes Burm. f. of the Myrsinaceae fam- [0100] The herbs are taken in the above proportion and ily, 15 grams, Rhizomes of Cyperus rotundus L., (Syno- powdered. Thepowders are mixed to getthe composition nym: Cyperus rotundus L. ssp. tuberosus (Rottb.) of the Example 1. The composition prepared as de- Kuekenth; and Cyperus tuberosus Rottb.) of the Cyper- scribed above is dispensed as sachets containing 6 aceae family, 50 grams, Fruits without seeds of Termi- 5 grams in it. The content of the sachet is to be added to nalia chebula (Gaertn.) Retz. of the Combretaceae fam- one and half to two liters of water in a suitable vessel and ily, 170 grams, Whole plant of Centella asiatica (L.) Urban boiled for two minutes. Then the powdered composition of the Apiaceae family, 10 grams, Stem with bark of Co- is to be strained and removed from the vessel to be dis- scinium fenestratum (Gaertn.) Colebr. of the Menisper- pensed off. The water so made is to be completely used maceae family, 50 grams, and Fruits with seeds of Zizy- 10 up by the diabetic patient in twenty four hours, using it phus jujuba Lamk. (Synonym: Zizyphus mauritiana instead of drinking water, in 8 or 6 divided doses. Lamk.) of the Rhamnaceae family, 25 grams. [0096] The herbs are taken in the above proportion Example 5: mixed and made into coarse powder using a pulveriser. The powder so made is extracted using water as a sol- 15 [0101] As per this example ; 100 grams of the formu- vent. Water from the resultant extract is completely evap- lation is made using 25 grams each of Dried fruits of orated to get dried flakes of the extract which is then Emblica officinalis , Dried roots of Salacia oblonga, , again powdered to get fine powder of the composition Dried rhizomes of Curcuma longa, ,and 15 grams of which makes up the active ingredient part of the formu- Seeds of Sizygium cumini and 5 grams each of Dried lation of the invention described in this Example 3. 20 leaves or seeds or seeds kernels of Mangifera indica , [0097] This active ingredient powder of the formulation Dried tuberous roots of Cyclea peltata. constitutes 0.625 grams of the 1 gram tablets. The rest [0102] The specified parts of the above mentioned of the 0.375 grams of each of the 1 gram tablet is con- herbs were taken in the above mentioned proportion and stituted by binders and exciepients of which some are powdered. The powders were mixed to get the formula- digestive, flavoring and absorptive adjuvants. The com- 25 tion. The formulation prepared as described above is dis- position of the exciepients and binders in a 1 gram tablet pensed as sachets containing 6 grams in each sachet. is 0.022 grams of Ipomoea batatas, 0.017 grams of Elet- When used the content of the sachet is to be added to taria cardamom, 0.023 grams of Piper longum, 0.0145 one and half to two liters of water in a suitable vessel and grams of Cuminum ciminum 0.016 grams of Di-calcium boiled for two minutes. Then the powdered composition Phosphate IP, 0.015 grams of PVPK-30, 0.0004 grams 30 is to be strained and removed from the vessel to be dis- each of Methyl paraben IP, Propyl paraben IP and col- pensed off. The water so made is to be completely used loidal silicon dioxide-IP, 0.0003 grams of talcum powder, up by the diabetic patient in twenty four hours, in 8 or 6 0.001 gram of Magnesium Stearate, 0.06 grams of Mi- divided doses. crocrystalline cellulose powder, 0.2 grams of IPA-IP and 0.005 grams of Aspartame, together constituting 0.375 35 Example 6: grams. Tablets are made using these ingredients in the above said ratio and in the conventional methods of tablet [0103] In this Example 6 of the invention, 100 grams making. of the composition is made using 30 grams each, Dried [0098] The above embodiment of the formulation as a rhizomes of Curcuma longa, and Dried fruits of Emblica tablet is orally administered to the diabetic patients as 40 officinalis and 10 grams each of Dried roots of Salacia one tablet, four times a day. The tablet is to be sublin- oblonga, Seeds of Sizygium cumini, and Dried tuberous gually placed to dissolve over ten minutes before food or roots of Cyclea peltata, and Dried seeds kernels of Man- to be chewed and swallowed by the patient within ten gifera indica. minutes after food. [0104] The herbs are taken in the above proportion 45 mixed and made into coarse powder using a pulveriser. Examples of the process of the preparation of herbal The powder so made is extracted using water as a sol- formulation used for the prevention and treatment of vent. Water from the resultant extract is completely evap- diabetes: orated to get dried flakes of the extract which is then again powdered to get fine powder of the composition Example 4: 50 which makes up the active ingredient part of the formu- lation of the invention described in this Example 6. [0099] As per this Example, 100 grams of the formu- [0105] This active ingredient powder of the formulation lation is made by using 20 grams each of Dried fruits of constitutes 0.625 grams of the 1 gram tablets. The rest Emblica officinalis, Dried roots of Salacia oblonga, Dried of the 0.375 grams of each of the 1 gram tablet is con- rhizomes of Curcuma longa, dried leaves or seeds or 55 stituted by binders and exciepients of which some are seeds kernels of Mangifera indica and 10 grams each of digestive, flavoring and absorptive adjuvants. The com- dried tuberous roots of Cyclea peltata and Seeds of Sizy- position of the exciepients and binders in a 1 gram tablet gium cumini. is 0.022 grams of Ipomoea batatas, 0.017 grams of Elet-

18 33 EP 2 326 338 B1 34 taria cardamom, 0.023 grams of Piper longum, 0.0145 is to be strained and removed from the vessel to be dis- grams of Cuminum ciminum 0.016 grams of Di-calcium pensed off. The water so made is to be completely used Phosphate IP, 0.015 grams of PVPK-30, 0.0004 grams up by the diabetic patient in twenty four hours, in 8 or 6 each of Methyl paraben IP, Propyl paraben IP and col- divided doses. loidal silicon dioxide-IP, 0.0003 grams of talcum powder, 5 0.001 gram of Magnesium Stearate, 0.06 grams of Mi- Example 9: crocrystalline cellulose powder, 0.2 grams of IPA-IP and 0.005 grams of Aspartame, together constituting 0.375 [0111] In this Example 9 of the invention, 100 grams grams. Tablets are made using these ingredients in the of the composition is made using 40 grams of Dried whole above said ratio and in the conventional methods of tablet 10 plant of Aerva lanata and 30 grams of Seeds of Strychnos making. potatorum and 10 grams each of Dried rhizomes of Cy- [0106] The above embodiment of the formulation as a perus rotundus, Dried roots of Vetiveria zizaniodes and tablet is orally administered to the diabetic patients as Dried tuberous roots of Cyclea peltata. one tablet, four times a day. The tablet is to be sublin- [0112] The herbs are taken in the above proportion gually placed to dissolve over ten minutes before food or 15 mixed and made into coarse powder using a pulveriser. to be chewed and swallowed by the patient within ten The powder so made is extracted using water as a sol- minutes after food. vent. Water from the resultant extract is completely evap- orated to get dried flakes of the extract which is then Examples of process for preparation of herbal formula- again powdered to get fine powder of the composition tion for prevention and treatment of renal complica- 20 which makes up the active ingredient part of the formu- tions associated with diabetes: lation of the invention described in this Example 9. [0113] This active ingredient powder of the formulation Example 7: constitutes 0.625 grams of the 1 gram tablets. The rest of the 0.375 grams of each of the 1 gram tablet is con- [0107] As per this Example, 100 grams of the formu- 25 stituted by binders and exciepients of which some are lation is made by using 20 grams each of Dried Seeds digestive, flavoring and absorptive adjuvants. The com- of Strychnos potatorum , Dried roots of Vetiveriaposition of the exciepients and binders in a 1 gram tablet zizaniodes , dried whole plant of Aerva lanata, dried tu- is 0.022 grams of Ipomoea batatas, 0.017 grams of Elet- berous roots of Cyclea peltata and Dried rhizomes of taria cardamom, 0.023 grams of Piper longum, 0.0145 Cyperus rotundus. 30 grams of Cuminum ciminum 0.016 grams of Di-calcium [0108] The herbs are taken in the above proportion and Phosphate IP, 0.015 grams of PVPK-30, 0.0004 grams powdered. The powders are mixed to get the composition each of Methyl paraben IP, Propyl paraben IP and col- of the Example 1. The composition prepared as de- loidal silicon dioxide-IP, 0.0003 grams of talcum powder, scribed above is dispensed as sachets containing 6 0.001 gram of Magnesium Stearate, 0.06 grams of Mi- grams in it. The content of the sachet is to be added to 35 crocrystalline cellulose powder, 0.2 grams of IPA-IP and one and half to two liters of water in a suitable vessel and 0.005 grams of Aspartame, together constituting 0.375 boiled for two minutes. Then the powdered composition grams. Tablets are made using these ingredients in the is to be strained and removed from the vessel to be dis- abovesaid ratioand in the conventional methodsof tablet pensed off. The water so made is to be completely used making. up by the diabetic patient in twenty four hours, using it 40 [0114] The above embodiment of the formulation as a instead of drinking water, in 8 or 6 divided doses. tablet is orally administered to the diabetic patients as one tablet, four times a day. The tablet is to be sublin- Example 8: gually placed to dissolve over ten minutes before food or to be chewed and swallowed by the patient within ten [0109] As per this example; 100 grams of the formula- 45 minutes after food. tion is made using 30 grams each Dried roots of Vetiveria zizaniodes, Seeds of Strychnos potatorum and Dried Examples of process for preparation of the herbal whole plant of Aerva lanata and 5 grams each of Dried formulation used for the prevention and treatment of rhizomes of Cyperus rotundus and Dried tuberous roots retinopathy associated with diabetes: of Cyclea peltata. 50 [0110] The specified parts of the above mentioned Example 10: herbs were taken in the above mentioned proportion and powdered. The powders were mixed to get the formula- [0115] As per this Example, 100 grams of the formu- tion. The formulation prepared as described above is dis- lation is made by using 25 grams each of Dried fruits of pensed as sachets containing 25 grams in each sachet. 55 Emblica officinafis, Seeds of Strychnos potatorum , Dried When used the content of the sachet is to be added to rhizomes of Curcuma longa, and dried Stem with bark of one and half to two liters of water in a suitable vessel and Coscinium fenestratum. boiled for two minutes. Then the powdered composition [0116] The herbs are taken in the above proportion and

19 35 EP 2 326 338 B1 36 powdered. The powders are mixed to get the composition colloidal silicon dioxide-IP, 0.0003 grams of talcum pow- of the Example 1. The composition prepared as de- der, 0.001 gram of Magnesium Stearate, 0.06 grams of scribed above is dispensed as sachets containing 8 Microcrystalline cellulose powder, 0.2 grams of IPA-IP grams in it. The content of the sachet is to be added to and 0.005 grams of Aspartame, together constituting one and half to two liters of water in a suitable vessel and 5 0.375 grams. Tablets are made using these ingredients boiled for two minutes. Then the powdered composition in the above said ratio and in the conventional methods is to be strained and removed from the vessel to be dis- of tablet making. pensed off. The water so made is to be completely used [0122] The above embodiment of the formulation as a up by the diabetic patient in twenty four hours, using it tablet is orally administered to the diabetic patients as instead of drinking water, in 8 or 6 divided doses. 10 one tablet, four times a day. The tablet is to be sublin- gually placed to dissolve over ten minutes before food or Example 11: to be chewed and swallowed by the patient within ten minutes after food. [0117] As per this example; 100 grams of the formula- tion is made using 30 grams each of Dried fruits of Em- 15 Examples for the process of preparation for herbal blica officinalis and Dried rhizomes of Curcuma longa formulationfor prevention and treatment of oxidative and 20 grams each of Seeds of Strychnos potatorum and damage to heart and its blood vessels associated dried Stem with bark of Coscinium fenestratum. with diabetes: [0118] The specified parts of the above mentioned herbs were taken in the above mentioned proportion and 20 Example 13: powdered. The powders were mixed to get the formula- tion. The formulation prepared as described above is dis- [0123] As per this Example, 100 grams of the formu- pensed as sachets containing 10 grams in each sachet. lation is made by using 20 grams each of Dried roots of When used the content of the sachet is to be added to Salacia oblonga, dried leaves or seeds or seeds kernels one and half to two liters of water in a suitable vessel and 25 of Mangifera indica, Dried rhizomes of Cyperus boiled for two minutes. Then the powdered composition rotundus , Dried fruits of Terminalia chebula and dried is to be strained and removed from the vessel to be dis- Fruits with seeds and stem bark of Zizyphus jujuba. pensed off. The water so made is to be completely used [0124] The herbs are taken in the above proportion and up by the diabetic patient in twenty four hours, in 8 or 6 powdered. Thepowders are mixed to getthe composition divided doses. 30 of the Example 1. The composition prepared as de- scribed above is dispensed as sachets containing 6 Example 12: grams in it. The content of the sachet is to be added to one and half to two liters of water in a suitable vessel and [0119] In this Example 12 of the invention, 100 grams boiled for two minutes. Then the powdered composition of the composition is made using 20 grams each of Dried 35 is to be strained and removed from the vessel to be dis- fruits of Emblica officinalis and Dried rhizomes of Curcu- pensed off. The water so made is to be completely used ma longa and 30 grams each of Seeds of Strychnos po- up by the diabetic patient in twenty four hours, using it tatorum and dried Stem with bark of Coscinium fenestra- instead of drinking water, in 8 or 6 divided doses. tum. [0120] The herbs are taken in the above proportion 40 Example 14: mixed and made into coarse powder using a pulveriser. The powder so made is extracted using water as a sol- [0125] As per this example ; 100 grams of the formu- vent. Water from the resultant extract is completely evap- lation is made using 50 grams of Dried fruits of Terminalia orated to get dried flakes of the extract which is then chebula, 20 grams of Dried leaves or seeds or seeds again powdered to get fine powder of the composition 45 kernels of Mangifera indica and 10 grams each Dried which makes up the active ingredient part of the formu- roots of Salacia oblonga, Fruits with seeds and stem bark lation of the invention described in this Example 12. of Zizyphus jujuba and Dried rhizomes of Cyperus rotun- [0121] This active ingredient powder of the formulation dus The specified parts of the above mentioned herbs constitutes 0.625 grams of the 1 gram tablets. The rest were taken in the above mentioned proportion and pow- of the 0.375 grams of each of the 1 gram tablet is con- 50 dered. The powders were mixed to get the formulation. stituted by binders and exciepients of which some are The formulation prepared as described above is dis- digestive, flavoring and absorptive adjuvants. The com- pensed as packet with single dose content of 12.5 grams position of the exciepients and binders in a 1 gram tablet sachets containing 6 grams in each sachet. When used is 0.022 grams of Ipomoea batatas, 0.017 grams of Elet- the content of the sachet is to be added to one and half taria cardamom, 0.023 grams of Piper longum, 0.0145 55 to two liters of water in a suitable vessel and boiled for grams of Cuminum ciminum 0.016 grams of Di-calcium two minutes. Then the powdered composition is to be Phosphate IP, 0.015 grams of PVPK-30, 0.0004 grams strained and removed from the vessel to be dispensed each of Methyl paraben IP, G Propyl paraben IP and off. The water so made is to be completely used up by

20 37 EP 2 326 338 B1 38 the diabetic patient in twenty four hours, in 8 or 6 divided 3. reduces the total cholesterol levels, LDL choles- doses. terol levels, increases the HDL cholesterol levels, reduces VLDL cholesterol levels, the Serum Triglyc- Example 15: eride levels and thereby offers better management 5 of the lipid profile [0126] In this Example 15 of the invention, 100 grams 4. improves the renal health and function, decreases of the composition is made using 30 grams each of Dried the incidence of urinary tract infections, and reduces fruits of Terminalia chebula and Dried roots of Salacia serum creatinine levels. oblonga, 15 grams each of Dried rhizomes of Cyperus 5. reduces the size of the prostrate gland significantly rotundusand Dried fruitsof Zizyphus jujube and10 grams 10 in diabetic patients suffering from benign prostratic of Dried seed kernels of Mangifera indica. hypertrophy. [0127] The herbs are taken in the above proportion 6. reduces the pain and numbness associated with mixed and made into coarse powder using a pulveriser. peripheral neuropathy usually affecting diabetic pa- The powder so made is extracted using water as a sol- tients. vent. Water from the resultant extract is completely evap- 15 7. has significant medicinal values useful in improve- orated to get dried flakes of the extract which is then ment of insulin sensitivity, reduction of hyperglyc- again powdered to get fine powder of the composition emia, reduction in hypoglycemic drug dependency which makes up the active ingredient part of the formu- and improvement in the general health of diabetics. lation of the invention described in this Example 15. 8. is an equally good or significantly better option of [0128] This active ingredient powder of the formulation 20 prophylactic diabetic control for people with identi- constitutes 0.625 grams of the 1 gram tablets. The rest fied pre-diabetic conditions when compared with diet of the 0.375 grams of each of the 1 gram tablet is con- and exercise alone or as an adjuvant to diet and ex- stituted by binders and exciepients of which some are ercise. digestive, flavoring and absorptive adjuvants. The com- 9. is an equally good or significantly better option of position of the exciepients and binders in a 1 gram tablet 25 diabetic control for newly identified diabetics when is 0.022 grams of Ipomoea batatas, 0.017 grams of Elet- compared with diet and exercise alone or as an ad- taria cardamom, 0.023 grams of Piper longum, 0.0145 juvant to diet and exercise. grams of Cuminum ciminum 0.016 grams of Di-calcium 10. is an excellent adjuvant with other anti-diabetic Phosphate IP, 0.015 grams of PVPK-30, 0.0004 grams drugs and reduces the need of other hypoglycemics. each of Methyl paraben IP, Propyl paraben IP and col- 30 11. improves the cardiovascular health, reduces hy- loidal silicon dioxide-IP, 0.0003 grams of talcum powder, pertension, improves the ratio of the serum lipid pro- 0.001 gram of Magnesium Stearate, 0.06 grams of Mi- file and improves performance in exercise tolerance crocrystalline cellulose powder, 0.2 grams of IPA-IP and test of a diabetic cardiac patient. 0.005 grams of Aspartame, together constituting 0.375 12. prevents retinal damages, cataract and deterio- grams. Tablets are made using these ingredients in the 35 ration of vision usually associated with diabetes, thus above said ratio and in the conventional methods of tablet ensuring a better quality of life for them. making. 13. augments wound healing of diabetic ulcers as [0129] The above embodiment of the formulation as a evidenced by reduced time in complete healing of tablet is orally administered to the hypertensive patient these ulcers. as one tablet, four times a day. The tablet is to be sub- 40 14. can be made into diverse pharmaceutical prep- lingually placed to dissolve over ten minutes before food arations such as tablets, capsules, granules, herbal or to be chewed and swallowed by the patient within ten health drink, fermented herbal nutraceutical bever- minutes after food. age, high-fiber nutraceutical food stuff(s), inhalable herbal medicinal preparation(s), ocular prepara- Utility of the invention 45 tion(s), transdermal absorbable preparation(s) and the like. [0130] The main advantage of the invention, for the prevention and treatment of diabetes and associated [0131] Main advantage of the invention, for the preven- complications is that it provides safe and effective herbal tion and treatment of diabetes is that it provides safe and formulation which simultaneously reduces the blood glu- 50 effective herbal formulation which simultaneously reduc- cose levels of a diabetic as well as offer prevention and es the blood glucose levels of a diabetic as well as offer treatment for possible associated complications of dia- prevention for prediabetic pateints. The same formula- betes. The same formulation also: tion also:

1. reduces the blood glucose level and thereby offers 55 1. reduces the blood glucose level and thereby offers better control over diabetes mellitus. better control over diabetes mellitus. 2. offers good glycaemic control and reduces the gly- 2. offers good glycaemic control and reduces the gly- cosylation of hemoglobin. cosylation of hemoglobin.

21 39 EP 2 326 338 B1 40

3. offers an equally good or significantly better option e. can be made into diverse pharmaceutical prepa- for people with identified pre-diabetic conditions rations such as tablets, capsules, granules, herbal when compared with diet and exercise alone or as health drink, fermented herbal nutraceutical bever- an adjuvant to diet and exercise and a process for age, high-fiber nutraceutical food stuff(s), inhalable the preparation of the same. 5 herbal medicinal preparation(s), ocular prepara- 4. is an equally good or significantly better option of tion(s), transdermal absorbable preparation(s) and diabetic control for newly identified diabetics when the like. compared with diet and exercise alone or as an ad- juvant to diet and exercise. [0134] Another main advantage of invention for pre- 5. is an excellent adjuvant with other anti-diabetic 10 venting oxidative damage to heart and blood vessels is drugs and reduces the need of other hypoglycemics. that it provides safe and effective herbal formulation 6. can be made into diverse pharmaceutical prepa- which simultaneously prevents oxidative damage to rations such as tablets, capsules, granules, syrups, heart and its blood vessels and also reduces hyperten- herbal health drink, fermented herbal nutraceutical sion. The same formulation also: beverage, high-fiber nutraceutical food stuff(s), in- 15 halable herbal medicinal preparation(s), ocular prep- 1. reduces systolic and diastolic blood pressure and aration(s), transdermal absorbable preparation(s) thereby offers better control over hypertension. and the like. 2. offers good antioxidant support to cardiac muscles and blood vessels and prevents stress related oxi- [0132] Another main advantage of the invention for the 20 dative damage to it. prevention and treatment of renal complications associ- 3. has significant medicinal values useful reduction ated with diabetes is that it provides safe and effective in hypertensive drug dependency and improvement herbal formulation for prevention and treatment of renal in the general health of hypertensive patients. complications associated with diabetes which simultane- 4. is an equally good or significantly better option of ously reduces the reduce the elevated levels of serum 25 prophylactic blood pressure control for people with creatinine. The same formulation also: identified pre-hypertensive conditions when com- pared with diet and exercise alone or as an adjuvant 1. improves the renal cellular health and thereby re- to diet and exercise. duces the elevated levels of serum creatinine. 5. is an equally good or significantly better option of 2. improves the renal health and function, decreases 30 blood pressure control for newly identified hyperten- the incidence of urinary tract infections, and reduces sives when compared with diet and exercise alone serum creatinine levels. or as an adjuvant to diet and exercise. 3. is an excellent adjuvant with other renal supportive 6. is an excellent adjuvant with other anti-hyperten- drugs. sive drugs and reduces the need of other anti-hyper- 4. can be made into diverse pharmaceutical prepa- 35 tensives, considerably. rations such as tablets, capsules, granules, herbal 7. can be made into diverse pharmaceutical prepa- health drink, fermented herbal nutraceutical bever- rations such as tablets, capsules, granules, herbal age, high-fiber nutraceutical food stuff(s), inhalable health drink, fermented herbal nutraceutical bever- herbal medicinal preparation(s), ocular prepara- age, high-fiber nutraceutical food stuff(s), inhalable tion(s), transdermal absorbable preparation(s) and 40 herbal medicinal preparation(s), ocular prepara- the like. tion(s), transdermal absorbable preparation(s) and the like. [0133] Another main advantage of the invention for the prevention and treatment of diabetic retinopathy is that it it provides safe and effective herbal formulation which 45 Claims prevents, manages and treats retinopathy associated with diabetes and offers arrest to the progress of the dis- 1. A herbal formulation for prevention and treatment of ease. The same formulation also: the diabetes and associated complications compris- ing: a. arrests the progress of retinopathy associated with 50 diabetes. a) Fruits without seeds of the Species Emblica b. offers prevention of retinopathy associated with officinalis Gaertn. (Synonym: Phyllanthus Em- diabetes in diabetic patients. blica L.) of the Euphorbiaceae Family, 5 to 8% c. is an excellent adjuvant with other anti-diabetic by w /w; drugs. 55 b) Roots of Species of herbs of the Genus Sa- d. prevents retinal damages, cataract and deteriora- lacia of the of the Celastraceae family, 10 to 15% tion of vision usually associated with diabetes, thus by w /w; ensuring a better quality of life for them. c) Seeds of the Species Strychnos potatorum L.

22 41 EP 2 326 338 B1 42

f. of the Strychnaceae family, 5 to 8% by w /w; Heyne, and/or Salacia macrosperma Wight. d) Roots of theSpecies Vetiveria zizanioides (L.) Nash (Synonym: Andropogon squarrosus Hook 3. A herbal formulation according to claim 1, wherein f. (non L. f.) of the Poaceae family, 1 to 5% by the Species of the Genus Aerva of the Amaranthace- w /w; 5 aea family are Aerva lanata Juss., and/or Aerva java- e) Rhizomes of the Species Curcuma longa L. nica (Burm. f.) Juss. ex J. A. Schultes (Synonym: of the Zingiberaceae family, 5 to 8% by w/w; Aerva tomentosa Forsk., Aerva persica (Burm. f.) f) Whole plant of Species of herbs of the Genus Merrill). Aerva of the Amaranthaceae family, 5 to 8% by w /w; 10 4. A herbal formulation according to claim 1, wherein g) Whole plant of Species of herbs of the Genus the Species of the Genus Biophytum of the Oxali- Biophytum of the Oxalidaceae family, 1 to 5% daceae family are Biophytum sensitivum (L.) DC: by w /w; (Synonym: Oxalis sensitivum L.) and/or Biophytum h) Seeds of Species of herbs of the Genus Syzy- reinwardtii Edgw. & Hk. f. gium of the Myrtaceae family, 5 to 8% by w /w; 15 i) Seeds kernels of the Species Mangifera indica 5. A herbal formulation according to claim 1, wherein L. of the Anacardiaceae family, 1 to 5% by w /w; the Species of the Genus Syzygium of the Myrtaceae j) Tuberous roots of Species of herbs of the Ge- family are Syzygium cumini (L.) Skeels (Synonym: nus Cyclea and /or roots of the Genus Cissam- Eugenia jambolana Lam.) and/or Syzygium caryo- pelos of the Menispermaceae family, 1 to 5% by 20 phyllaeum Gaertn. (Synonym: Eugenia carophyl- w /w; laea Wt.). k) Seeds of Species of herbs of the Genus Em- belia of the Myrsinaceae family, 1 to 5% by w /w; 6. A herbal formulation according to claim 1, wherein l) Rhizomes of Species of herbs of the Genus the Species of the Genus Cyclea is Cyclea peltata Cyperus of the Cyperaceae family, 1 to 5% by 25 (Lam..) Hook. f. & Thorns, and/or Species of the Ge- w /w; nus Cissampelos is Cissampelos pareira L. of the m) Fruits without seeds of the Species Termi- Menispermaceae family. nalia chebula (Gaertn.) Retz. of the Combreta- ceae family, 15 to 30% by w /w; 7. A herbal formulation according to claim 1, wherein n) Whole plant of the Species Centella asiatica 30 the Species of the Genus Embelia of the Myrsinace- (L.) Urban of the Apiaceae family and ae family are Embelia ribes Burm. f. and/or Embelia / or leaves of the Species Strychnos nux-vomica tsjerium-cottam A. DC. (Synonym: Embelia robusta L. (Synonym: Strychnos ligustrina Blume) of the Clarke (non Roxb.). Strychnaceae family, and / or flowers of the Spe- cies Butea frondosa Koen. ex Roxb. (synonym: 35 8. A herbal formulation according to claim 1, wherein Butea monosperma (Lam.) Taub. of the Papil- the Species of the Genus Cyperus of the Cyperace- ionaceae family and /or heart wood of the Spe- ae family are Cyperus rotundus L, (Synonym: Cype- cies Acacia catechu (L.f.) Willd. of the Mi- rus rotundus L. ssp. tuberosus (Rottb.) Kuekenth; mosaceae family, 1 to 5% by w /w; and Cyperus tuberosus Rottb.) and/or Cyperus es- o) Stem with bark of the Species Coscinium fe- 40 culentus L. and/or Cyperus scariosus R. Br. nestratum (Gaertn.) Colebr. of the Menisperma- ceae family and / or stem with bark of Species 9. A herbal formulation according to claim 1, wherein of herbs of the Genus Berberis of the Berberi- the Species of the Genus Berberis of the Berberi- daceae family, 5 to 8% w/w and daceae family are DC. var. aristata p) Fruits with seeds and stem bark of Species 45 (Synonym: Berberis aristata Hook. f. & Thorns., Ber- of herbs of the Gen Zizyphusof the Rhamnaceae beris chitria Lindl.) and/or Berberis calliobotrys Aitch. family, 1 to 5% by w /w, wherein the ingredients ex Koehne and/or Berberis lycium Royle and/or Ber- are powdered to 1 millimeter to 3 millimeter par- berisorthobotrys Bien. ex. Aitch. and/or Berberisum- ticle size and blended in a blender at 30 to 60 bellata Wall, ex G. Don. and/or Berberis vulgaris L. rotations per minutes to obtain the homogenous 50 of the Berberidaceae family. herbal formulation. 10. An herbal formulation according to claim 1, wherein 2. A herbal formulation according to claim 1, wherein the Species of the Genus Zizyphus of the Rham- the Species of the Genus Salacia of the Celastrace- naceae family are Zizyphus jujuba Lamk. (Synonym: ae family are Salacia oblonga Wall, ex Wight & Arn. 55 Zizyphus mauritiana Lamk.), and/or Zizyphus xy- and/or, Salacia reticulata Wight and/or, Salacia chin- lopyrus (Retz.) Willd. (xylopyra, xylophora) and/or ensis L. (Synonym: Salacia latifolia Wall. ex. Laws; Zizyphus jujuba Mill. (Synonym: Zizyphus sativa Salacia prinoides DC.) and/or Salacia fruticosa Gaertn., Zizyphus vulgaris Lamk.) and/or Zizyphus

23 43 EP 2 326 338 B1 44

oenoplia (L.) Mill, and/or Zizyphus rugosa Lamk. , %; and/or Zizyphus glabrata Heyne ex Roth and/or Zizy- m) Früchte ohne Samen der Species Terminalia phus nummularia (Burm. f.) Wt. & Arn. chebula (Gaertn.) Retz. der Familie der Com- bretaceae, 15 bis 30 Gew.-%; 11. An herbal formulation according to claim 1, further 5 n)Ganze Pflanzender SpeciesCentella asiatica formulated to tablets or capsules or granules or syr- (L.) Urban der Familie der Apiaceae und / oder ups or herbal health drink or inhalable herbal medic- Blätter der Species Strychnos nux-vomica L. inal preparations or ocular preparations or transder- (Synonym: Strychnos ligustrina Blume) der Fa- mal absorbable preparations such as ointments / milie der Strychnaceae, und / oder Blüten der gels or injectable medicine. 10 Species Butea frondosa Koen. ex Roxb. (Syn- onym: Butea monosperma (Lam.) Taub. der Fa- 12. An herbal formulation according to claim 1, further milie der Papilionaceae und /oder Kernholz der containing suitable digestive, flavoring, binding, Species Acacia catechu (L.f.) Willd. der Familie sweetening and exciepient and / or absorptive adju- der Mimosaceae, 1 bis 5 Gew.-%; vants. 15 o) Stamm mit Rinde der Species Coscinium fe- nestratum (Gaertn.) Colebr. der Familie der Me- nispermaceae und / oder Stamm mit Rinde der Patentansprüche Kräuterspecies des Genus Berberis der Familie der Berberidaceae, 5 bis 8 Gew.-% und 1. Pflanzliche Formulierung zur Verhütung und Be-20 p) Früchte mit Samen und Stammrinde der handlung von Diabetes und damit verbundenen Kräuterspecies des Genus Zizyphus der Familie Komplikationen, umfassend: der Rhamnaceae, 1 bis 5 Gew.-%, wobei die Inhaltsstoffe zu einer Partikelgröße von 1 Milli- a) Früchte ohne Samen der Species Emblica meter bis 3 Millimeter pulverisiert werden und in officinalis Gaertn. (Synonym: Phyllanthus Em- 25 einem Mischer bei 30 bis 60 Umdrehungen pro blica L.) der Familie der Euphorbiaceae, 5 bis 8 Minute gemischt werden, um eine homogene Gew.-%; pflanzliche Formulierung zu erhalten. b) Wurzeln der Kräuterspecies des Genus Sa- lacia der Familie der Celastraceae, 10 bis 15 2. Pflanzliche Formulierung nach Anspruch 1, wobei Gew.-%; 30 die Species des Genus Salacia der Familie der Ce- c) Samen der Species Strychnos potatorum L. lastraceae Salacia oblonga Wall, ex Wight & Arn. f. der Familie der Strychnaceae f, 5 bis 8 Gew.- und/oder, Salacia reticulata Wight und/oder, Salacia %; chinensis L. (Synonym: Salacia latifolia Wall. ex. d) Wurzeln der Species Vetiveria zizanioides Laws; Salacia prinoides DC.) und/oder Salacia fru- (L.) Nash (Synonym: Andropogon squarrosus 35 ticosa Heyne, und/oder Salacia macrosperma Wight Hook f. (nicht L. f.) der Familie der Poaceae, 1 sind. bis 5 Gew.-%; e) Rhizome der Species Curcuma longa L. der 3. Pflanzliche Formulierung nach Anspruch 1, wobei Familie der Zingiberaceae, 5 to 8 Gew.-%; die Species des Genus Aerva der Familie der f) Ganze Pflanzen der Kräuterspecies des Ge- 40 Amaranthaceaea Aerva lanata Juss., und/oder Ae- nus Aerva der Familie der Amaranthaceae, 5 rva javanica (Burm. f.) Juss. ex J. A. Schultes (Syn- bis 8 Gew.-%; onym: Aerva tomentosa Forsk., Aerva persica g) Ganze Pflanzen der Kräuterspecies des Ge- (Burm. f.) Merrill) sind. nus Biophytum der Familie der Oxalidaceae, 1 bis 5 Gew.-%; 45 4. Pflanzliche Formulierung nach Anspruch 1, wobei h) Samen der Kräuterspecies des Genus Syzy- die Species des Genus Biophytum der Familie der gium derFamilie derMyrtaceae, 5 bis8 Gew.-%; Oxalidaceae Biophytum sensitivum (L.) DC: (Syno- i) Samenkeme der Species Mangifera indica L. nym: Oxalis sensitivum L.) und/oder Biophytum rein- der Familie der Anacardiaceae, 1 bis 5 Gew.-%; wardtii Edgw. & Hk. f. sind. j) Knollenwurzeln der Kräuterspecies des Ge- 50 nus Cyclea und /oder Wurzeln des Genus 5. Pflanzliche Formulierung nach Anspruch 1, wobei Cissampelos der Familie der Menispermaceae, die Species des Genus Syzygium der Familie der 1 bis 5 Gew.-%; Myrtaceae Syzygium cumini (L.) Skeels (Synonym: k) Samen der Kräuterspecies des Genus Em- Eugenia jambolana Lam.) und/oder Syzygium cary- belia der Familie der Myrsinaceae, 1 bis 5 Gew.- 55 ophyllaeum Gaertn. (Synonym: Eugenia carophylla- %; ea Wt.) sind. l) Rhizome der Kräuterspecies des Genus Cy- perus der Familie der Cyperaceae, 1 bis 5 Gew.- 6. Pflanzliche Formulierung nach Anspruch 1, wobei

24 45 EP 2 326 338 B1 46

die Species des Genus Cyclea Cyclea peltata a) les fruits sans graines de l’espèceEmblica (Lam..) Hook. f. & Thorns ist, und/oder die Species officinalis Gaertn. (synonyme : Phyllanthus Em- des Genus Cissampelos Cissampelos pareira L. der blica L.) de la famille des Euphorbiacées, à rai- Familie Menispermaceae ist. son de 5 % à 8 % en poids/poids ; 5 b) les racines d’espèces de plantes du genre 7. Pflanzliche Formulierung nach Anspruch 1, wobei Salacia de la famille des Célastracées, à raison the Species des Genus Embelia der Familie der Myr- de 10 % à 15 % en poids/poids ; sinaceae Embelia ribes Burm. f. und/oder Embelia c) les graines de l’espèce Strychnos potatorum tsjeriumcottam A. DC. (Synonym: Embelia robusta L. f. de la famille des Strychnacées, à raison de Clarke (non Roxb.) sind. 10 5 % à 8 % en poids/poids ; d) les racines de l’espèce Vetiveria zizanioides 8. Pflanzliche Formulierung nach Anspruch 1, wobei (L.) Nash (synonyme : Andropogon squarrosus die Species des Genus Cyperus Familie der Cyper- Hook f. (non L. f.) de la famille des Poacées, à aceae Cyperus rotundus L, (Synonym: Cyperus ro- raison de 1 % à 5 % en poids/poids ; tundus L. ssp. tuberosus (Rottb.) Kuekenth; und Cy- 15 e) les rhizomes de l’espèce Curcuma longa L. perus tuberosus Rottb.) und/oder Cyperus esculen- de la famille des Zingibéracées, à raison de 5 tus L. und/oder Cyperus scariosus R. Br sind. % à 8 % en poids/poids ; f) la plante entière d’espèces de plantes du gen- 9. Pflanzliche Formulierung nach Anspruch 1, wobei re Aerva de la famille des Amaranthacées, à rai- die Species des Genus Berberis der Familie der Ber- 20 son de 5 % à 8 % en poids/poids ; beridaceae Berberis aristata DC. var. aristata (Syn- g) la plante entière d’espèces de plantes du gen- onym: Berberis aristata Hook. f. & Thorns., Berberis re Biophytum de la famille des Oxalidacées, à chitria Lindl.) und/oder Berberis calliobotrys Aitch. raison de 1 % à 5 % en poids/poids ; ex Koehne und/oder Berberis lycium Royle und/oder h) les graines d’espèces de plantes du genre Berberis orthobotrys Bien. ex. Aitch. und/oder Ber- 25 Syzygium de la famille des Myrtacées, à raison beris umbellata Wall, ex G. Don. und/oder Berberis de 5 % à 8 % en poids/poids ; vulgaris L. der Familie der Berberidaceae sind. i) les noyaux de l’espèce Mangifera indica L. de la famille des Anacardiacées, à raison de 1 % à 10. Pflanzliche Formulierung nach Anspruch 1, wobei 5 % en poids/poids ; die Species des Genus Zizyphus der Familie der 30 j) les racines tubéreuses d’espèces de plantes Rhamnaceae Zizyphus jujuba Lamk. (Synonym: Zi- du genre Cyclea et/ou les racines du genre Cis- zyphus mauritiana Lamk.), und/oder Zizyphus xylo- sampelos de la famille des Ménispermacées, à pyrus (Retz.) Willd. (xylopyra, xylophora) und/oder raison de 1 % à 5 % en poids/poids ; Zizyphus jujuba Mill. (Synonym: Zizyphus sativa Ga- k) les graines d’espèces de plantes du genre ertn., Zizyphus vulgaris Lamk.) und/oder Zizyphus 35 Embelia de la famille des Myrsinacées, à raison oenoplia (L.) Mill, und/oder Zizyphus rugosa Lamk. , de 1 % à 5 % en poids/poids ; und/oder Zizyphus glabrata Heyne ex Roth und/oder l) les rhizomes d’espèces de plantes du genre Zizyphus nummularia (Burm. f.) Wt. & Arn sind. Cyperus de la famille des Cyperacées, à raison de 1 % à 5 % en poids/poids ; 11. Pflanzliche Formulierung nach Anspruch 1, wobei 40 m) les fruits sans graines de l’espèce Terminalia sie weiter formuliert ist als Tabletten oder Kapseln chebula (Gaertn.) Retz. de la famille des Com- oder Granulat oder Sirupe oder pflanzlicher Gesund- brétacées, à raison de 15 % à 30 % en heitstrank oder inhalierbare pflanzenmedizinische poids/poids ; Präparationen oder oculare Präparationen oder n) la plante entière de l’espèce Centella asiatica transdermal absorbierbare Präparationen, bei-45 (L.) Urban de la famille des Apiacées et/ou les spielsweise Salben / Gele oder injizierbare Arznei. feuilles de l’espèce Strychnos nux-vomica L. (synonyme : Strychnos ligustrina Blume) de la 12. Pflanzliche Formulierung nach Anspruch 1, wobei famille des Strychnacées et/ou les fleurs de l’es- sie desweiteren geeignete verdauungsfördernde pèce Butea frondosa Koen. ex Roxb. Mittel, Aromastoffe, Bindemittel, Süßstoffe und Hilfs- 50 (synonyme : Butea monosperma (Lam.) Taub. stoffe und/oder absorptive Adjuvantien, enthält. de la famille des Papilionacées et/ou le duramen de l’espèce Acacia catechu (L.f.) Willd. de la fa- mille des Mimosacées, à raison de 1 % à 5 % Revendications en poids/poids ; 55 o) la tige avec l’écorce de l’espèceCoscinium 1. Formulation à base de plantes servant à prévenir et fenestratum (Gaertn.) Colebr. de la famille des à traiter le diabète et les complications associées, Ménispermacées et/ou la tige avec l’écorce comprenant : d’espèces de plantes du genre Berberis de la

25 47 EP 2 326 338 B1 48

famille des Berbéridacées, à raison de 5 % à 8 sus R. Br. % en poids/poids et p) les fruits avec les graines et l’écorce de la tige 9. Formulation à base de plantes selon la revendication d’espèces de plantes du genre Zizyphus de la 1, dans laquelle les espèces du genre Berberis de famille des Rhamnacées, à raison de 1 % à 5 5 la famille des Berbéridacées sont Berberis aristata % en poids/poids, dans laquelle les ingrédients DC. var. aristata (synonyme : Berberis aristata sont sous la forme d’une poudre ayant une taille Hook. f. & Thorns., Berberis chitria Lindl.) et/ou Ber- de particule de 1 millimètre à 3 millimètres et beris calliobotrys Aitch. ex Koehne et/ou Berberis mélangés dans un mélangeur à une vitesse de lycium Royle et/ou Berberis orthobotrys Bien. ex. rotation de 30 à 60 tours par minute pour obtenir 10 Aitch. et/ou Berberis umbellata Wall, ex G. Don. la formulation homogène à base de plantes. et/ou Berberis vulgaris L. de la famille des Berbéri- dacées. 2. Formulation à base de plantes selon la revendication 1, dans laquelle les espèces du genre Salacia de la 10. Formulation à base de plantes selon la revendication famille des Célastracées sont Salacia oblonga Wall, 15 1, dans laquelle les espèces du genre Zizyphus de ex Wight & Arn. et/ou Salacia reticulata Wight et/ou la famille des Rhamnacées sontZizyphus jujuba Salacia chinensis L. (synonyme :Salacia latifolia Lamk. (synonyme : Zizyphus mauritiana Lamk.), Wall. ex. Laws ; Salacia prinoides DC.) et/ou Salacia et/ou Zizyphus xylopyrus (Retz.) Willd. (xylopyra, xy- fruticosa Heyne et/ou Salacia macrosperma Wight. lophora) et/ou Zizyphus jujuba Mill. (synonyme : Zi- 20 zyphus sativa Gaertn., Zizyphus vulgaris Lamk.) 3. Formulation à base de plantes selon la revendication et/ou Zizyphus oenoplia (L.) Mill et/ou Zizyphus ru- 1, dans laquelle les espèces du genre Aerva de la gosa Lamk. et/ou Zizyphus glabrata Heyne ex Roth famille des Amaranthacées sont Aerva lanata Juss. et/ou Zizyphus nummularia (Burm. f.) Wt. & Arn. et/ou Aerva javanica (Burm. f.) Juss. ex J. A. Schul- tes (synonyme : Aerva tomentosa Forsk., Aerva per- 25 11. Formulation à base de plantes selon la revendication sica (Burm . f.) Merrill). 1, formulée en outre sous la forme de comprimés ou de capsules ou de granulés ou de sirop ou d’une 4. Formulation à base de plantes selon la revendication boisson de santé à base de plantes ou de prépara- 1, dans laquelle les espèces du genre Biophytum de tions médicinales inhalables à base de plantes ou la famille des Oxalidacées sont Biophytum sensiti- 30 de préparations oculaires ou de préparations absor- vum (L.) DC. (synonyme : Oxalis sensitivum L.) et/ou bables à travers la peau, comme des pomma- Biophytum reinwardtii Edgw. & Hk. f. des/gels, ou d’un médicament injectable.

5. Formulation à base de plantes selon la revendication 12. Formulation à base de plantes selon la revendication 1, dans laquelle les espèces du genre Syzygium de 35 1, contenant en outre un agent digestif, aromatisant, la famille des Myrtacées sont Syzygium cumini (L.) liant, édulcorant et excipient approprié et/ou des ad- Skeels (synonyme : Eugenia jambolana Lam.) et/ou juvants d’absorption. Syzygium caryophyllaeum Gaertn. (synonyme : Eugenia carophyllaea Wt.). 40 6. Formulation à base de plantes selon la revendication 1, dans laquelle l’espèce du genre Cyclea est Cyclea peltata (Lam..) Hook. f. & Thorns et/ou l’espèce du genre Cissampelos est Cissampelos pareira L. de la famille des Ménispermacées. 45

7. Formulation à base de plantes selon la revendication 1, dans laquelle les espèces du genreEmbelia de la famille des Myrsinacées sont Embelia ribes Burm. f. et/ou Embelia tsjerium-cottam A. DC. (synonyme : 50 Embelia robusta Clarke (non Roxb.).

8. Formulation à base de plantes selon la revendication 1, dans laquelle les espèces du genre Cyperus de la famille des Cypéracées sont Cyperus rotundus L., 55 (synonyme : Cyperus rotundus L. ssp. tuberosus (Rottb.) Kuekenth; et Cyperus tuberosus Rottb.) et/ou Cyperus esculentus L. et/ou Cyperus scario-

26 EP 2 326 338 B1

REFERENCES CITED IN THE DESCRIPTION

This list of references cited by the applicant is for the reader’s convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.

Patent documents cited in the description

• EP 20050779434 A [0021] • WO 02089825 A [0024] • KR 20020011015 [0022] • JP 2006056836 B [0066] • CA 2532332 [0023]

Non-patent literature cited in the description

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